Immunogenetics pp 635-680 | Cite as

Human Gm, Km, and Am Allotypes and Their Molecular Characterization: A Remarkable Demonstration of Polymorphism

  • Marie-Paule Lefranc
  • Gérard Lefranc
Part of the Methods in Molecular Biology book series (MIMB, volume 882)


Human immunoglobulin allotypes are antigenic determinants (or “markers”) determined serologically, classically by hemagglutination inhibition, on the human immunoglobulin (IG) heavy and light chains. The allotypes have been identified on the gamma1, gamma2, gamma3, and alpha2 heavy chains (they are designated as G1m, G2m, G3m, and A2m allotypes, respectively), and on the kappa light chain (Km allotypes). Gm-Am allotypes are inherited in fixed combinations, or Gm-Am haplotypes, owing to the linkage of the human IGHC genes (IGHG3, IGHG1, IGHA1, IGHG2, IGHG4, IGHE, and IGHA2 from 5′ to 3′ in the IGH locus on chromosome 14). Gm and Am allotypes have been one of the most powerful tools in population genetics and very instrumental in molecular characterization of the human IGHC genes (gene conversion, copy number variation, gene order). They represent a major system for understanding immunogenicity of the polymorphic IG chains, in relation with amino acid and conformational changes. The correlation between G3m allotypes and amino acid changes has been possible with the sequencing of many alleles of the IGHG3 gene, from individuals from different populations and with known allotypes. In this chapter, we integrate genetics and sequence data and provide an updated overview of the Gm-Am haplotypes and Km allotypes. We propose, for the first time, a complete elucidation of the G3m allotypes, illustrated by the “IMGT G3m allele butterfly” concept that allows a graphical representation of the G3m alleles (variants of a gene expressing a given set of allotypes). Knowledge of allotypes is important in antibody engineering and humanization of monoclonal antibodies to improve immunotherapy.

Key words

IMGT Immunogenetics Allotype Haplotype Gm Km Am Gm-Am Immuno-informatics Immunoglobulin Antibody Allelic polymorphism IMGT-ONTOLOGY 



We thank Géraldine Folch for the “IMGT G3m allele butterfly” representation, Chantal Ginestoux and Saida Hadi-Saljoqi for their help, and François Ehrenmann for the 3D structure figures. We are very grateful to the IMGT® team for its expertise and constant motivation. This chapter is a tribute to Erna van Loghem, Liliane Rivat and Claude Ropartz.


  1. 1.
    Lefranc M-P, Lefranc G (1990) Molecular genetics of immunoglobulin allotype expression. In: Shakib F (ed) The human IgG subclasses: molecular analysis of structure, function and regulation (chapter 4). Pergamon, Oxford, UK, pp 43–78Google Scholar
  2. 2.
    Lefranc M-P (2011) Antibody nomenclature: from IMGT-ONTOLOGY to INN definition. MAbs 3(1):1–2PubMedGoogle Scholar
  3. 3.
    Jefferis R, Lefranc M-P (2009) Human immunoglobulin allotypes: possible implications for immunogenicity. MAbs 1(4):332–338PubMedGoogle Scholar
  4. 4.
    Magdelaine-Beuzelin C, Vermeire S, Goodall M, Baert F, Noman M, Van Assche G, Ohresser M, Degenne D, Dugoujon JM, Jefferis R, Rutgeerts P, Lefranc M-P, Watier H (2009) IgG1 heavy chain-coding gene polymorphism (G1m allotypes) and development of antibodies-to-infliximab. Pharmacogenet Genomics 19:383–387PubMedGoogle Scholar
  5. 5.
    Lefranc M-P (2008) IMGT®, the international ImMunoGeneTics information system® for immunoinformatics. Methods for querying IMGT® databases, tools and Web resources in the context of immunoinformatics. Mol Biotechnol 40:101–111PubMedGoogle Scholar
  6. 6.
    Lefranc M-P, Giudicelli V, Ginestoux C, Jabado-Michaloud J, Folch G, Bellahcene F, Wu Y, Gemrot E, Brochet X, Lane J, Regnier L, Ehrenmann F, Lefranc G, Duroux P (2009) IMGT®, the international ImMunoGeneTics information system®. Nucleic Acids Res 37:D1006–D1012PubMedGoogle Scholar
  7. 7.
    Giudicelli V, Lefranc M-P (1999) Ontology for immunogenetics: IMGT-ONTOLOGY. Bioinformatics 15:1047–1054PubMedGoogle Scholar
  8. 8.
    Duroux P, Kaas Q, Brochet X, Lane J, Ginestoux C, Lefranc M-P, Giudicelli V (2008) IMGT-Kaleidoscope, the formal IMGT-ONTOLOGY paradigm. Biochimie 90:570–583PubMedGoogle Scholar
  9. 9.
    Lefranc M-P, Giudicelli V, Regnier L, Duroux P (2008) IMGT®, a system and an ontology that bridge biological and computational spheres in bioinformatics. Brief Bioinform 9:263–275PubMedGoogle Scholar
  10. 10.
    Lefranc M-P (2000) Nomenclature of the human immunoglobulin genes. In: Coligan JE, Bierer BE, Margulies DE, Shevach EM, Strober W (eds) Current protocols in immunology. Wiley, Hoboken, NJ, pp A.1P.1–A.1P.37Google Scholar
  11. 11.
    Lefranc G, Lefranc M-P (2001) The immunoglobulin FactsBook. Academic Press, London, UK, pp 1–458Google Scholar
  12. 12.
    Lefranc M-P (2007) WHO-IUIS nomenclature subcommittee for immunoglobulins and T cell receptors report. Immunogenetics 59:899–902PubMedGoogle Scholar
  13. 13.
    Lefranc M-P (2008) WHO-IUIS nomenclature subcommittee for immunoglobulins and T cell receptors report August 2007, 13th Inter­national Congress of Immunology, Rio de Janeiro, Brazil. Dev Comp Immunol 32:461–463PubMedGoogle Scholar
  14. 14.
    Lefranc M-P, Pommié C, Kaas Q, Duprat E, Bosc N, Guiraudou D, Jean C, Ruiz M, Da Piédade I, Rouard M, Foulquier E, Thouvenin V, Lefranc G (2005) IMGT unique numbering for immunoglobulin and T cell receptor constant domains and Ig superfamily C-like domains. Dev Comp Immunol 29:185–203PubMedGoogle Scholar
  15. 15.
    Giudicelli V, Chaume D, Lefranc M-P (2005) IMGT/GENE-DB: a comprehensive database for human and mouse immunoglobulin and T cell receptor genes. Nucleic Acids Res 33:D256–D261PubMedGoogle Scholar
  16. 16.
    Kaas Q, Ruiz M, Lefranc M-P (2004) IMGT/3Dstructure-DB and IMGT/StructuralQuery, a database and a tool for ­immunoglobulin, T cell receptor and MHC structural data. Nucleic Acids Res 32:D208–D210PubMedGoogle Scholar
  17. 17.
    Ehrenmann F, Kaas Q, Lefranc M-P (2010) IMGT/3Dstructure-DB and IMGT/DomainGapAlign: a database and a tool for immunoglobulins or antibodies, T cell receptors, MHC, IgSF and MhcSF. Nucleic Acids Res 38:D301–D307PubMedGoogle Scholar
  18. 18.
    Kaas Q, Lefranc M-P (2007) IMGT Colliers de Perles: standardized sequence-structure representations of the IgSF and MhcSF superfamily domains. Curr Bioinform 2:21–30Google Scholar
  19. 19.
    Kaas Q, Ehrenmann F, Lefranc M-P (2007) IG, TR and IgSf, MHC and MhcSF: what do we learn from the IMGT Colliers de Perles? Brief Funct Genomic Proteomic 6:253–264PubMedGoogle Scholar
  20. 20.
    Grubb R (1956) Agglutination of erythrocytes coated with “incomplete” anti-Rh by certain rheumatoid arthritic sera and some other sera. The existence of human serum groups. Acta Pathol Microbiol Scand 39:195–197PubMedGoogle Scholar
  21. 21.
    Grubb R, Laurell AB (1956) Hereditary serological human serum groups. Acta Pathol Microbiol Scand 39:390–398PubMedGoogle Scholar
  22. 22.
    Harboe M, Lundevall J (1959) A new type in the Gm system. Acta Pathol Microbiol Scand 45:357–370PubMedGoogle Scholar
  23. 23.
    Steinberg AG, Wilson JA (1963) Studies on hereditary gamma globulin factors: evidence that Gm (b) in Whites and Negroes is not the same and that Gm-like is determined by an allele at the Gm locus. Am J Hum Genet 15:96–105PubMedGoogle Scholar
  24. 24.
    Gold ER, Ropartz C, Rivat L, Rousseau PY (1965) Gm(f)–a determinant of human gamma-globulin. Vox Sang 10:299–302PubMedGoogle Scholar
  25. 25.
    Gold ER, Mandy WJ, Fudenberg HH (1965) Relation between Gm(f) and the structure of the gamma-globulin molecule. Nature 207(5001):1099–1101PubMedGoogle Scholar
  26. 26.
    Litwin SD, Kunkel HG (1966) A gamma-globulin genetic factor related to Gm(a) but localized to a different portion of the same heavy chains. Nature 210:866PubMedGoogle Scholar
  27. 27.
    Kunkel HG, Yount WJ, Litwin SD (1966) Genetically determined antigen of the Ne subgroup of gamma-globulin: detection by precipitin analysis. Science 154(752):1041–1043PubMedGoogle Scholar
  28. 28.
    Harboe M (1959) A new hemagglutinating substance in the Gm system, anti-Gmb. Acta Pathol Microbiol Scand 47:191–198PubMedGoogle Scholar
  29. 29.
    Steinberg AG, Giles BD, Stauffer R (1960) A Gm-like factor present in Negroes and rare or absent in whites: its relation to Gma and Gmx. Am J Hum Genet 12:44–51PubMedGoogle Scholar
  30. 30.
    Ropartz C, Rivat L, Rousseau PY (1963) Le Gm(b) et ses problèmes. Vox Sang 8:717–723PubMedGoogle Scholar
  31. 31.
    Steinberg AG, Goldblum R (1965) A genetic study of the antigens associated with the Gm(b) factor of human γ-globulin. Am J Hum Genet 17:133–147PubMedGoogle Scholar
  32. 32.
    Martensson L, van Loghem E, Matsumoto H, Nielsen J (1966) Gm(s) and Gm(t): genetic determinants of human gamma-globulin. Vox Sang 11:393–418PubMedGoogle Scholar
  33. 33.
    Natvig JB (1966) Gm(g)–a “new” gamma-globulin factor. Nature 211:318–319PubMedGoogle Scholar
  34. 34.
    van Loghem E, Martensson L (1967) Genetic (Gm) determinants of the γ2c (Vi) subclass of human IgG immunoglobulins. A study with special reference to Gm(c3) and Gm(c5), and their relationship with the Gm(b) ­determinants. Vox Sang 13:369–392PubMedGoogle Scholar
  35. 35.
    van Loghem E, Grobbelaar BG (1971) A new genetic marker of human IgG3 immunoglobulin. Evolutionary dissociation of Gm allotypes. Vox Sang 21:405Google Scholar
  36. 36.
    Schanfield MS, Fudenberg HH (1974) Gm (Ray), a new allotypic marker on human IgG3. Vox Sang 26:133–140PubMedGoogle Scholar
  37. 37.
    Blanc M, Dugoujon JM, Ruffié J (1976) [A new genetic marker for human IgG3 usually associated with Gm (21) factor found in the caucasian and mongolian populations]. In French. Un nouveau marqueur génétique des IgG3 humaines habituellement associé au facteur Gm(21) dans les populations caucasoides et mongoloides. C R Acad Sci Paris 283:1461–1463Google Scholar
  38. 38.
    van Loghem E, Blanc M, de Lange G (1977) Human IgG3 allotypes, with special reference to a new allotype related to G3m(g) (G3m(21)). J Immunogenet 4:371–383PubMedGoogle Scholar
  39. 39.
    Vyas GN, Fudenberg HH (1969) Am(1), the first genetic marker of human immunoglobulin A. Proc Natl Acad Sci USA 64:1211–1216PubMedGoogle Scholar
  40. 40.
    Kunkel HG, Smith WK, Joslin FG, Natvig JB, Litwin SD (1969) Genetic marker of the gamma-A2 subgroup of γA immunoglobulins. Nature 223:1247–1248PubMedGoogle Scholar
  41. 41.
    van Loghem E, Wang AC, Shuster J (1973) A new genetic marker of human immunoglobulins determined by an allele at the α2 locus. Vox Sang 24:481–488PubMedGoogle Scholar
  42. 42.
    Ropartz C, Lenoir J, Rivat L (1961) A new inheritable property of human sera: the Inv factor. Nature 189:586–587PubMedGoogle Scholar
  43. 43.
    Ropartz C, Rivat L, Rousseau PY (1962) Deux nouveaux facteurs dans les systèmes héréditaires de gammaglobuline: le Gm(e) et l’Inv(l). Proceedings of the 9th Society of blood Transfusion. Karger Baset, Mexico, p 455Google Scholar
  44. 44.
    Steinberg AG, Wilson JA, Lanset S (1962) A new human gamma globulin factor determined by an allele at the Inv locus. Vox Sang 7:151–156PubMedGoogle Scholar
  45. 45.
    WHO (1976) Review of the notation for the allotypic and related markers of human immunoglobulins. WHO meeting on human immunoglobulin allotypic markers. J Immunogenet 3:357–362Google Scholar
  46. 46.
    WHO. Review of the notation for the allotypic and related markers of human immunoglobulins (1976) WHO meeting on human immunoglobulin allotypic markers, held July 16–19, 1974, Rouen, France. Report amended June 1976. Eur J Immunol 6:599Google Scholar
  47. 47.
    Lefranc G, Loiselet J, Rivat L, Ropartz C (1976) Gm, Km and ISf allotypes in the Lebanese population. Acta Anthropogenet 1:34–45Google Scholar
  48. 48.
    Lefranc G, Rivat L, Rivat C, Loiselet J, Ropartz C (1976) Evidence for “deleted” or “silent” genes homozygous at the locus coding for the constant region of the γ3 chain. Am J Hum Genet 28:51–61PubMedGoogle Scholar
  49. 49.
    Lefranc G, Rivat L, Salier JP, van Loghem E, Aydenian H, Zalzal P, Chakhachiro L, Loiselet J, Ropartz C (1977) Recombination, mutation, or constitutive expression at a Gm locus and familial hypergammaglobulinemia. Am J Hum Genet 29:523–536PubMedGoogle Scholar
  50. 50.
    Lefranc G (1978) Allotypes et haplotypes des immunoglobulines dans les communautés libanaises: intérêt exceptionnel en immunogénétique et séro-anthropologie [in French]. PhD Thesis. Université de Rouen, FranceGoogle Scholar
  51. 51.
    Lefranc G (1978) Immunoglobulin allotypes and haplotypes in the Lebanese communities: discussion of unusual genetic events and population structure. PhD Thesis. Université de Rouen, France, pp 1–137Google Scholar
  52. 52.
    Lefranc G, Rivat L, Serre JL, Lalouel JM, Pison G, Loiselet J, Ropartz C, de Lange G, van Loghem E (1978) Common and uncommon immunoglobulin haplotypes among Lebanese communities. Hum Genet 41:197–209PubMedGoogle Scholar
  53. 53.
    Lefranc G, de Lange G, Rivat L, Langaney A, Lefranc M-P, Ellouze F, Sfar G, Sfar M, van Loghem E (1979) Gm, Am and Km immunoglobulin allotypes of two populations in Tunisia. Hum Genet 50:199–211PubMedGoogle Scholar
  54. 54.
    Ropartz C, Rivat L, Rousseau PY, Baitsch H, van Loghem J (1963) The Gm and Inv systems in Europe. Acta Genet Stat Med 13:109–123PubMedGoogle Scholar
  55. 55.
    Ropartz C, Rousseau PY, Rivat L (1963) Les groupes de gamma-globulines Gm et Inv : Etude génétique et anthropologique. Bull Soc Anthropol Paris 4(Xie ser.):458–469Google Scholar
  56. 56.
    Steinberg AG, Matsumoto H (1964) Studies on the Gm, Inv, Hp and Tf serum factors of Japanese populations and families. Hum Biol 36:77–85PubMedGoogle Scholar
  57. 57.
    Taleb N, Ruffie J (1968) Hémotypologie des populations jordaniennes. Bull Mém Soc Anthrop Paris 3(XIIe sér.):269–282Google Scholar
  58. 58.
    Ropartz C, Rivat L, Rousseau PY, Lauridsen UB, Persson I (1970) A survey of 9 Gm-factors, the Inv and the ISf systems in Danes. Hum Hered 20:275–280PubMedGoogle Scholar
  59. 59.
    Jenkins T, Zoutendyk A, Steinberg AG (1970) Gammaglobulin groups (Gm and Inv) of various Southern African populations. Am J Phys Anthropol 32:197–218PubMedGoogle Scholar
  60. 60.
    Mayr WR, Mickerts D (1970) Der menschliche Gammaglobulin-Polymorphismus. Acta Biol Med Germ 25:475–482Google Scholar
  61. 61.
    Bonné B, Godber M, Ashbel S, Mourant AE, Tills D (1971) South-Sinai Beduin. A preliminary report on their inherited blood factors. Am J Phys Anthropol 34:397–408PubMedGoogle Scholar
  62. 62.
    Ropartz C, Rivat L, Rousseau PY, Legueult LC (1972) Frequency of Gm, Inv and ISf phenotypes in the population of 4 Yugoslavian villages. Hum Hered 22:508–518PubMedGoogle Scholar
  63. 63.
    Salzano FM, Steinberg AG, Tepfenhart MA (1973) Gm and Inv allotypes of Brazilian Cayapo Indians. Am J Hum Genet 25:167–177PubMedGoogle Scholar
  64. 64.
    Steinberg AG (1973) Contribution of the Gm and Inv allotypes to the characterization of human populations. Israel J Med Sci 9:1249–1256PubMedGoogle Scholar
  65. 65.
    Steinberg AG (1973) Gm and Inv allotypes of some Sidamo Ethiopians. Am J Phys Anthropol 39:403–408PubMedGoogle Scholar
  66. 66.
    Wiebecke D (1973) Die frequenczen von Gm (1,2,3,5) und Inv (1) in der Bevölkerung der Bundesrepublik Deustchland. Humangenetik 18:175–180PubMedGoogle Scholar
  67. 67.
    Fraser GR, Volkers WS, Bernini LF, van Loghem E, Meera Khan P, Nijenhuis LE (1974) Gene frequencies in a Dutch population. Hum Hered 24:435–448PubMedGoogle Scholar
  68. 68.
    Daveau M, Rivat L, Langaney A, Afifi N, Bois E, Ropartz C (1975) Gm and Inv allotypes in French Guiana Indians. Hum Hered 25:88–92PubMedGoogle Scholar
  69. 69.
    Schanfield MS, Gergely J, Fudenberg HH (1975) Immunoglobulin allotypes of European populations. I. Gm and Km(Inv) allotypic markers in Hungarians. Hum Hered 25:370–377PubMedGoogle Scholar
  70. 70.
    Schanfield MS, Herzog P, Fudenberg HH (1975) Immunoglobulin allotypes of European populations. II.Gm, Am and Km(Inv) allotypic markers in Czechoslovakians. Hum Hered 25:382–392PubMedGoogle Scholar
  71. 71.
    Steinberg AG, Jenkins T, Nurse GT, Harpending HC (1975) Gammaglobulin groups of the Khoisan peoples of Southern Africa: evidence for polymorphism for a Gm1,5,13,14,21 haplotype among the San. Am J Hum Genet 27:528–542PubMedGoogle Scholar
  72. 72.
    Lalouel JM, Loiselet J, Lefranc G, Chaiban D, Chakhachiro L, Rivat L, Ropartz C (1976) Genetic differentiation among Lebanese communities. Acta Anthropogenet 1:15–33Google Scholar
  73. 73.
    Piazza A, van Loghem E, de Lange G, Curtoni ES, Ulizzi L, Terrenato L (1976) Immunoglobulin allotypes in Sardinia. Am J Hum Genet 28:77–86PubMedGoogle Scholar
  74. 74.
    Gershowitz H, Neel JV (1978) The immunoglobulin allotypes (Gm and Km) of twelve Indian tribes of Central and South America. Am J Phys Anthropol 49:289–301PubMedGoogle Scholar
  75. 75.
    Rivat L, Rivat C, Cook CE, Steinberg AG (1978) Gm(28). Un nouvel allotype du système Gm présent sur les IgG3: Intérêt particulier de son étude dans les populations négroides. Ann Immunol Inst Pasteur 129:33–45Google Scholar
  76. 76.
    Steinberg AG, Cook CE (1981) The distribution of the human immunoglobulin allotypes. Oxford University Press, OxfordGoogle Scholar
  77. 77.
    Chaabani H, Helal AN, van Loghem E, Langaney A, Benammar Elgaaied A, Rivat Peran L, Lefranc G (1984) Genetic study of Tunisian Berbers. I. Gm, Am and Km immunoglobulin allotypes and ABO blood groups. J Immunogenet 11:107–113PubMedGoogle Scholar
  78. 78.
    de Lange G, Zhong FM, Henke J, Feng ZC, Bernhardt R, van Leeuwen F, van Eede P (1985) Immunoglobulin allotypes in a Chinese population: comparison of haplotype frequencies with other Asian groups. J Immunogenet 12:191–195PubMedGoogle Scholar
  79. 79.
    van Loghem E (1986) Immunoglobulin markers. In: Cavalli-Sforza LL (ed) African pygmies (chapter 14). Academic Press, Orlando, p 201Google Scholar
  80. 80.
    Helal AN, Rivat-Peran L, van Loghem E, de Lange G, Langaney A, Lefranc G (1988) Further contribution of common Gm-Am haplotypes and Km alleles in the characterization of the Tunisian population. Exp Clin Immunogenet 5:1–14PubMedGoogle Scholar
  81. 81.
    Helal AN, de Lange G, van Loghem E, Lefranc G (1988) Uncommon Gm haplotypes in the Tunisian population: further contribution to the genetics of the IgG immunoglobulins. Exp Clin Immunogenet 5:24–38PubMedGoogle Scholar
  82. 82.
    Soua Z, Ghanem N, Salem B, Lefranc G, Lefranc M-P (1989) Frequencies of the human immunoglobulin IGHA2*M1 and IGHA2*M2 alleles corresponding to the A2m(1) and A2m(2) allotypes in the French, Lebanese, Tunisian and Black African populations. Nucleic Acids Res 17:3625PubMedGoogle Scholar
  83. 83.
    Zhao TM, Lee TD (1989) Gm and Km allotypes in 74 Chinese populations: a hypothesis of the origin of the Chinese nation. Hum Genet 83:101–110PubMedGoogle Scholar
  84. 84.
    Blanc M, Sanchez-Mazas A, Van Blyenburgh NH, Sevin A, Pison G, Langaney A (1990) Interethnic genetic differentiation: Gm polymorphism in eastern Senegal. Am J Hum Genet 46:383–392PubMedGoogle Scholar
  85. 85.
    Sukernik RI, Osipova LP, Schanfield MS (1992) Distribution of GM allotypes and deleted IGHG1 haplotypes in the Sel’kups in comparison to the Forest Nentsi of northwestern Siberia. Exp Clin Immunogenet 9:15–23PubMedGoogle Scholar
  86. 86.
    Schanfield MS (1992) Immunoglobulin ­allotypes (GM and KM) indicate multiple founding populations of Native Americans: evidence of at least four migrations to the New World. Hum Biol 64:381–402PubMedGoogle Scholar
  87. 87.
    Yacoubi Loveslati B, Sanchez-Mazas A, Ennafaa H, Marrakchi R, Dugoujon J-M, Lefranc M-P, Ben Ammar Elgaaied A (2001) A study of Gm allotypes and immunoglobulin heavy gamma chain IGHG genes in Berbers, Arabs and sub-Saharan Africans from Jerba Island, Tunisia. Eur J Immunogenet 28:531–538Google Scholar
  88. 88.
    Geha RS, Malakian A, Lefranc G, Chaiban D, Serre JL (1976) Immunologic reconstitution in severe combined immunodeficiency following transplantation with parental bone marrow. Pediatrics 58:451–455PubMedGoogle Scholar
  89. 89.
    van Loghem E, Natvig JB (1970) Uncommon Gm gene complexes. Vox Sang 18:421–434PubMedGoogle Scholar
  90. 90.
    van Loghem E, Natvig JB, Matsumoto H (1970) Genetic markers of immunoglobulins in Japanese families. Inheritance of associated markers belonging to one IgA and three IgG subclasses. Ann Hum Genet 33:351–359Google Scholar
  91. 91.
    Lefranc G, Dumitresco SM, Salier JP, Rivat L, de Lange G, van Loghem E, Loiselet J (1979) Familial lack of the IgG3 subclass: gene elimination or turning off expression and neutral evolution in the immune system. J Immunogenet 6:215–221PubMedGoogle Scholar
  92. 92.
    Salier JP, Rivat L, Daveau M, Lefranc G, Breton P, De Menibus CH, Henocq A, Fudenberg HH (1980) Quantitative studies of Gm allotypes. V. Simultaneous presence of latent Gm allotypes and deficient Gm genes in a family with hypogammaglobulinaemic probands. J Immunogenet 7:123–135PubMedGoogle Scholar
  93. 93.
    van Loghem E, Sukernik RI, Osipova LP, Zegers BJM, Matsumoto H, De Lange G, Lefranc G (1980) Gene deletion and gene duplication within the cluster of human heavy chain genes. Selective absence of IgG sub-classes. J Immunogenet 7:285–299PubMedGoogle Scholar
  94. 94.
    Lefranc M-P (1980) Les allotypes Gm, Am et Km des immunoglobulines humaines dans deux échantillons de la population Tunisienne (Mahdia et Sfax): contribution à la connaissance séro-anthropologique de cette population et à la génétique des immunoglobulines [in French] Thesis, Série 3° cycle n°16, Université Paris Sud, France, pp 1–108Google Scholar
  95. 95.
    Lefranc G, Lefranc M-P, Helal AN, Boukef K, Chaabani H, Gandoura MS, van Loghem E (1982) Unusual heavy chains of human IgG immunoglobulins: rearrangements of the CH domain exons. J Immunogenet 9:1–9PubMedGoogle Scholar
  96. 96.
    van Loghem E, de Lange G, van Leeuwen AM, van Eede PH, Nijenhuis LE, Lefranc M-P, Lefranc G (1982) Human IgG allotypes co-occurring in more than one IgG subclass. Vox Sang 43:301–309PubMedGoogle Scholar
  97. 97.
    Lefranc M-P, Lefranc G, Rabbitts TH (1982) Inherited deletion of immunoglobulin heavy chain constant region genes in normal human individuals. Nature 300:760–762PubMedGoogle Scholar
  98. 98.
    Lefranc M-P, Lefranc G, de Lange G, Out TA, van den Broek PJ, van Nieuwkoop J, Radl J, Helal AN, Chaabani H, van Loghem E, Rabbitts TH (1983) Instability of the human immunoglobulin heavy chain constant region locus indicated by different inherited chromosomal deletions. Mol Biol Med 1:207–217PubMedGoogle Scholar
  99. 99.
    Lefranc G, Chaabani H, van Loghem E, Lefranc M-P, de Lange G, Helal AN (1983) Simultaneous absence of the human IgG1, IgG2, IgG4 and IgA1 subclasses: immunological and immunogenetical considerations. Eur J Immunol 13:240–244PubMedGoogle Scholar
  100. 100.
    Flanagan JG, Lefranc M-P, Rabbitts TH (1984) Mechanisms of divergence and convergence of the human immunoglobulin alpha1 and alpha2 constant region gene sequences. Cell 36:681–688PubMedGoogle Scholar
  101. 101.
    Lefranc M-P, Rabbitts TH (1984) Human immunoglobulin heavy chain A2 gene allotype determination by restriction fragment length polymorphism. Nucleic Acids Res 12:1303–1311PubMedGoogle Scholar
  102. 102.
    Lefranc M-P (1984) Recombinaisons, délétions et conversions de gènes de la région constante des chaînes lourdes des immunoglobulines humaines [in French]. PhD Thesis. Université Montpellier 2, FranceGoogle Scholar
  103. 103.
    Lefranc M-P, Helal AN, de Lange G, Chaabani H, van Loghem E, Lefranc G (1986) Gene conversion in human immunoglobulin γ locus shown by unusual location of IgG allotypes. FEBS Lett 196:96–102PubMedGoogle Scholar
  104. 104.
    Huck S, Fort P, Crawford DH, Lefranc M-P, Lefranc G (1986) Sequence of a human immunoglobulin γ3 heavy chain constant region gene: comparison with the other human Cγ genes. Nucleic Acids Res 14:1779–1789PubMedGoogle Scholar
  105. 105.
    Lefranc M-P, Lefranc G (1987) Human immunoglobulin heavy-chain multigene deletions in healthy individuals. FEBS Lett 213:231–237PubMedGoogle Scholar
  106. 106.
    Huck S, Lefranc G, Lefranc M-P (1989) A human immunoglobulin IGHG3 allele (Gmb0, b1, c3, c5, u) with an IGHG4 converted region and three hinge exons. Immunogenetics 30:250–257PubMedGoogle Scholar
  107. 107.
    Keyeux G, Lefranc G, Lefranc M-P (1989) A multigene deletion in the human IGH constant region locus involves highly homologous hot spots of recombination. Genomics 5:431–441PubMedGoogle Scholar
  108. 108.
    Lefranc M-P, Hammarström L, Smith CI, Lefranc G (1991) Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis. Immunodefic Rev 2:265–281PubMedGoogle Scholar
  109. 109.
    Bensmana M, Chuchana P, Lefranc G, Lefranc M-P (1991) Sequence of the CH1 and hinge-CH2 exons of the human immunoglobulin IGHA2 A2m(2) allele: comparison with the nonallelic and allelic IGHA genes. Cytogenet Cell Genet 56:128PubMedGoogle Scholar
  110. 110.
    Lefranc M-P, Hammarström L, Smith CIE, Lefranc G (1993) Gene deletions in the human immunoglobulin heavy chain constant region locus: molecular and immunological analysis. In: Rosen FS, Seligmann M (eds) Immunodeficiencies (chapter 5). Harwood Academic Publishers, Newark, New Jersey, USA, pp 99–109Google Scholar
  111. 111.
    Wiebe V, Helal A, Lefranc M-P, Lefranc G (1994) Molecular analysis of the T17 immunoglobulin CH multigene deletion (del A1-GP-G2-G4-E). Hum Genet 93:520–528PubMedGoogle Scholar
  112. 112.
    Dard P, Huck S, Frippiat JP, Lefranc G, Langaney A, Lefranc M-P, Sanchez-Mazas A (1997) The IGHG3 gene shows a structural polymorphism characterized by different hinge lengths: sequence of a new 2-exon hinge gene. Hum Genet 99:138–141PubMedGoogle Scholar
  113. 113.
    Dard P, Lefranc M-P, Osipova L, Sanchez-Mazas A (2001) DNA sequence variability of IGHG3 alleles associated to the main G3m haplotypes in human populations. Eur J Hum Genet 9:765–772PubMedGoogle Scholar
  114. 114.
    Flanagan JG, Rabbitts TH (1982) Arrangement of human immunoglobulin heavy chain constant region genes implies evolutionary duplication of a segment containing γ, ε and α genes. Nature 300:709–713PubMedGoogle Scholar
  115. 115.
    Rabbitts TH, Flanagan JG, Lefranc M-P (1983) Flexibility and change within the human immunoglobulin gene locus. In: Chater KF et al (eds) Genetic rearrangement. Croom Helm, London, UK, pp 143–154Google Scholar
  116. 116.
    Ghanem N, Lefranc M-P, Lefranc G (1988) Definition of the RFLP alleles in the human immunoglobulin IGHG gene locus. Eur J Immunol 18:1059–1065PubMedGoogle Scholar
  117. 117.
    Ghanem N, Dugoujon JM, Bensmana M, Huck S, Lefranc M-P, Lefranc G (1988) Restriction fragment haplotypes in the human immunoglobulin IGHG locus and their correlation with the Gm polymorphism. Eur J Immunol 18:1067–1072PubMedGoogle Scholar
  118. 118.
    Ghanem N, Dugoujon JM, Lefranc M-P, Lefranc G (1989) BstEII restriction fragment alleles and haplotypes of the human IGHG genes with reference to the BamHI/SacI RFLPs and to the Gm polymorphism. Exp Clin Immunogenet 6:39–54PubMedGoogle Scholar
  119. 119.
    Ghanem N, Bensmana M, Dugoujon JM, Constans J, Lefranc M-P, Lefranc G (1989) BamHI and SacI RFLPs of the human immunoglobulin IGHG genes with reference to the Gm polymorphism in African people. Evidence for a major polymorphism. Hum Genet 83:37–4418PubMedGoogle Scholar
  120. 120.
    Hammarström L, Ghanem N, Smith CIE, Lefranc G, Lefranc M-P (1990) RFLP of human immunoglobulin genes. Exp Clin Immunogenet 7:7–19PubMedGoogle Scholar
  121. 121.
    Dard P, Sanchez-Mazas A, Dugoujon JM, de Lange G, Langaney A, Lefranc M-P, Lefranc G (1996) DNA analysis of the immunoglobulin IGHG loci in a Mandenka population from eastern Senegal: correlation with Gm haplotypes and hypotheses for the evolution of the Ig CH region. Hum Genet 98:36–47PubMedGoogle Scholar
  122. 122.
    Osipova LP, Posukh OL, Wiebe VP, Miyazaki T, Matsumoto H, Lefranc G, Lefranc M-P (1999) BamHI-SacI RFLP and Gm analysis of the immunoglobulin IGHG genes in the Northern Selkups (west Siberia): new haplotypes with deletion, duplication and triplication. Hum Genet 105:530–541PubMedGoogle Scholar
  123. 123.
    Gold ER, Fudenberg HH (1967) Chromic chloride: a coupling reagent for passive hemagglutination reactions. J Immunol 99(5): 859–866PubMedGoogle Scholar
  124. 124.
    de Lange G (1988) Monoclonal antibodies against human immunoglobulin allotypes. PhD Thesis. London, Amsterdam, pp 1–175Google Scholar
  125. 125.
    Zelaschi D, Newby C, Parsons M, van West B, Cavalli-Sforza LL, Herzenberg LA, Herzenberg LA (1983) Human immunoglobulin allotypes: previously unrecognized determinants and alleles defined with monoclonal antibodies. Proc Natl Acad Sci USA 80:3762–3766PubMedGoogle Scholar
  126. 126.
    Kurth JH, Bowcock AM, Erlich HA, Nevo S, Cavalli-Sforza LL (1991) Km typing with PCR: application to population screening. Am J Hum Genet 48(3):613–620PubMedGoogle Scholar
  127. 127.
    Balbin M, Grubb A, Abrahamson M, Grubb R (1991) Determination of allotypes G1m (f) and G1m (z) at the genomic level by subclass-specific amplification of DNA and use of allele-specific probes. Exp Clin Immunogenet 8:88–95PubMedGoogle Scholar
  128. 128.
    Balbin M, Grubb A, de Lange GG, Grubb R (1994) DNA sequences specific for Caucasian G3m (b) and (g) allotypes: allotyping at the genomic level. Immunogenetics 39:187–193PubMedGoogle Scholar
  129. 129.
    Brusco A, de Lange GG, Boccazzi C, Carbonara AO (1995) Molecular characterization of G2m (n+) and G2m (n-)allotypes. Immunogenetics 42:414–417PubMedGoogle Scholar
  130. 130.
    Hougs L, Svejgaard A, Barington T (2001) The first constant-domain (CH1) exon of human IGHG2 is polymorphic and in strong linkage disequilibrium with the (CH2) exon polymorphism encoding the G2m(n+) allotype in Caucasians. Immunogenetics 52:242–248PubMedGoogle Scholar
  131. 131.
    Frangione B, Franklin EC, Fudenberg HH, Koshland ME (1966) Structural studies of human γG myeloma proteins of different antigenic subgroups and genetic specificities. J Exp Med 124:715–732PubMedGoogle Scholar
  132. 132.
    Press EM, Hogg NM (1970) The amino-acid sequences of the Fd fragments of two human γ1 heavy chains. Biochem J 117:641–660PubMedGoogle Scholar
  133. 133.
    Burton RM, Deutsch HF (1970) The structure of peptides of Fc-fragments from γG-globulins of known allotypic specificity. Immunochemistry 7:145–156PubMedGoogle Scholar
  134. 134.
    Natvig JB, Turner MW (1971) Localization of Gm markers to different molecular regions of the Fc fragment. Clin Exp Immunol 8:685–700PubMedGoogle Scholar
  135. 135.
    Michaelsen TE, Frangione B, Franklin EC (1977) The amino acid sequence of a human immunoglobulin G3m(g) pFc’ fragment. J Immunol 119:558–563PubMedGoogle Scholar
  136. 136.
    Pardo AG, Rosenwasser ES, Frangione B (1978) The primary structure of a human immunoglobulin G2 (IgG2) pFc’fragment. J Immunol 121:1040–1044PubMedGoogle Scholar
  137. 137.
    Natvig JB, Kunkel HG, Joslin FG (1969) Delineation of two antigenic markers, “non a” and “non g” related to the genetic antigens of human gamma globulins. J Immunol 102:611–617PubMedGoogle Scholar
  138. 138.
    Kunkel HG, Joslin FG, Penn GM, Natvig JB (1970) Genetic variants of γG4 globulin. A unique relationship to other classes of γG globulin. J Exp Med 13:508–520Google Scholar
  139. 139.
    van Loghem E, de Lange G (1972) ‘non-b’, antigenic determinant of IgG. Vox Sang 22:193–199PubMedGoogle Scholar
  140. 140.
    Gaarder PI, Natvig JB (1972) Two new antigens of human IgG, “non b0” and “non b1”, related to the Gm system. J Immunol 108:617–621PubMedGoogle Scholar
  141. 141.
    van Loghem E, de Lange G (1976) The first example of an isoallotype of human IgG located on the Fd fragment. Scand J Immunol 5:1015–1019PubMedGoogle Scholar
  142. 142.
    van Loghem E, de Lange G, Koistinen J (1976) The first isoallotype of human IgA proteins. An antigenic determinant occurring as allotype in the IgA2 subclass and as isotype in the IgA1 subclass. Scand J Immunol 5:161–164PubMedGoogle Scholar
  143. 143.
    van Loghem E (1971) Formal genetics of the immunoglobulin systems. Ann N Y Acad Sci 190:136–149PubMedGoogle Scholar
  144. 144.
    Wang AC, Shuster J, Fudenberg HH (1969) Evolutionary origin of the Gm“a” peptide of immunoglobulins. J Mol Biol 41:83–86PubMedGoogle Scholar
  145. 145.
    Cook CE, Steinberg AG (1979) An amino acid substitution in the γ1 chain of human immunoglobulin G associated with the Gm (2) allotype. Mol Immunol 16:555–558PubMedGoogle Scholar
  146. 146.
    Wolfenstein-Todel C, Frangione B, Prelli F, Franklin EC (1976) The amino acid sequence of “heavy chain disease” protein ZUC. Structure of the Fc fragment of immunoglobulin G3. Biochem Biophys Res Commun 71:907–914PubMedGoogle Scholar
  147. 147.
    Frangione B, Rosenwasser E, Prelli F, Franklin EC (1980) Primary structure of human γ3 immunoglobulin deletion mutant: γ3 heavy-chain disease protein Wis. Biochemistry 19:4304–4308PubMedGoogle Scholar
  148. 148.
    Alexander A, Steinmetz M, Barritault D, Frangione B, Franklin EC, Hood L, Buxbaum JN (1982) Gamma heavy chain disease in man: cDNA sequence supports partial gene deletion model. Proc Natl Acad Sci USA 79(10):3260–3264PubMedGoogle Scholar
  149. 149.
    Recht B, Frangione B, Franklin E, van Loghem E (1981) Structural studies of a human γ3 myeloma protein (GOE) that binds Staph protein A. J Immunol 127:917–923PubMedGoogle Scholar
  150. 150.
    Matsumoto H, Ito S, Miyazaki T, Ohta T (1983) Structural studies of a human γ3 myeloma protein (JIR) bearing the allotypic marker Gm(st). J Immunol 131: 1865–1870PubMedGoogle Scholar
  151. 151.
    Matsumoto H, Ito S, Miyazaki T, Kawai N (1986) Structural studies of another human IgG3 myeloma protein (Kam) carrying the allotypic markers Gm(s,t) and its alteration induced by chemical modification. In: Brinkmann B, Henningsen K (eds) Advances in forensic haemogenetics, Springer Verlag, Berlin-Heidelberg, Germany vol I. p 153Google Scholar
  152. 152.
    Abel CA, Despont JP (1974) An amino acid deletion associated with the IgG4b allotype of human IgG4 myeloma proteins. J Immunogenet 1:79–82Google Scholar
  153. 153.
    Tsuzukida Y, Wang CC, Putnam FW (1979) Structure of the A2m(1) allotype of human IgA. A recombinant molecule. Proc Natl Acad Sci USA 76:1104–1108PubMedGoogle Scholar
  154. 154.
    Toraño A, Putnam FW (1978) Complete amino acid sequence of the alpha 2 heavy chain of a human IgA2 immunoglobulin of the A2m (2) allotype. Proc Natl Acad Sci USA 75(2):966–969PubMedGoogle Scholar
  155. 155.
    Flanagan JG, Lefranc M-P, Rabbitts TH (1984) Mechanisms of divergence and convergence of the human immunoglobulin alpha 1 and alpha 2 constant region gene sequences. Cell 36(3):681–688PubMedGoogle Scholar
  156. 156.
    Baglioni C, Alescio Zonta L, Cioli D, Carbonara A (1966) Allelic antigenic factor Inv(a) of the light chains of human immunoglobulins: chemical basis. Science 152:1517–1519PubMedGoogle Scholar
  157. 157.
    Steinberg AG, Milstein CP, McLaughlin CL, Solomon A (1974) Structural studies of an Inv (1, -2) kappa light chain. Immunogenetics 2:1–10Google Scholar
  158. 158.
    Milstein CP, Steinberg AG, McLaughlin CL, Solomon A (1974) Amino acid sequence change associated with genetic marker Inv(2) of human immunoglobulin. Nature 248:160–161PubMedGoogle Scholar
  159. 159.
    van Loghem E, Aalberse RC, Matsumoto H (1984) A genetic marker of human IgE heavy chains, Em(1). Vox Sang 46:195–206PubMedGoogle Scholar
  160. 160.
    Ghanem N, Dariavach P, Bensmana M, Chibani J, Lefranc G, Lefranc M-P (1988) Polymorphism of immunoglobulin lambda constant region genes in populations from France, Lebanon and Tunisia. Exp Clin Immunogenet 5:186–195PubMedGoogle Scholar
  161. 161.
    Lefranc M-P, Lefranc G (1992) Les Immunoglobulines humaines. In: Breton-Gorius J, Reyes F, Rochant H, Rosa J, Vernant JP (eds) L’hématologie de Bernard Dreyfus (chapter 20). Médecine-Sciences Flammarion, pp 197–254Google Scholar
  162. 162.
    Lefranc M-P, Pallarès N, Frippiat J-P (1999) Allelic polymorphisms and RFLP in the human immunoglobulin lambda light chain locus. Hum Genet 104:361–369PubMedGoogle Scholar
  163. 163.
    Lefranc M-P, Lefranc G (2004) Immunoglo­bulin lambda (IGL) genes of human and mouse. In: Honjo T, Alt FW, Neuberger MS (eds) Molecular biology of B cells. Academic Press, Elsevier Science Amsterdam, The Netherlands, pp 37–59Google Scholar
  164. 164.
    Goetze AM, Zhang Z, Liu L, Jacobsen FW, Flynn GC (2011) Rapid LC-MS screening for IgG Fc modifications and allelic variants in blood. Mol Immunol 49:338–352Google Scholar
  165. 165.
    Liu YS, Low TL, Infante A, Putnam FW (1976) Complete covalent structure of a human IgA1 immunoglobulin. Science 193(4257):1017–1020PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.IMGT®, The International ImMunoGeneTics Information System®Université Montpellier 2, Laboratoire d’ImmunoGénétique Moléculaire (LIGM), Institut de Génétique Humaine (IGH), UPR CNRS1142MontpellierFrance

Personalised recommendations