Journal of Clinical Immunology

, Volume 10, Issue 5, pp 223–236 | Cite as

Pairing of VK and VK gene families in self-reactive antibodies

  • Constantin A. Bona
  • Yukiko Saitoh
  • Garnett Kelson
Special Article

Key words

Autoantibodies V gene Ly1 autoantigens monoclonal antibodies 


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  1. 1.
    Brodeur P, Osman GE, Mackle JJ, Lalor, TM: The organization of the mouse Igh-V locus. J Exp Med 168:2261–2278, 1988.Google Scholar
  2. 2.
    D'Hoostelaere LA, Huppi K, Mock B, Malett C, Potter M: The Igk L chain allelic groups among the Igk haplotypes and Igk cross over population suggest a gene order. J Immunol 141:652–661, 1988Google Scholar
  3. 3.
    Perlmutter RM: The molecular gentices of phosphocholine binding antibodies.In The Biology of Idiotypes, M Green, A Nisonoff (eds). New York, Plenum Press, p 53, 1984Google Scholar
  4. 4.
    Victor-Kobrin C, Barak ZT, Bonilla FA, Kobrin B, Sanz I, French D, Rothe J, Bona C: A molecular and structural analysis of the VH and VK regions of monoclonal antibodies bearing the A48 regulatory idiotype. J Immunol 144:614–624, 1990Google Scholar
  5. 5.
    Pawlita M, Potter M, Rudikoff S: K-chain restriction in anti-galactan antibodies. J Immunol 129:615–618, 1982Google Scholar
  6. 6.
    Schilling J, Clevinger B, Davie J, Hood L: Amino-acid sequence of homogeneous antibodies to dextran and DNA rearrangements in heavy chain V-region segments. Nature 283:35–40, 1980Google Scholar
  7. 7.
    Vrana M, Rudikoff S, and Potter M: Sequence variation among heavy chain from inulin binding myeloma proteins. Proc Natl Acad Sci 75:1957–1961, 1978Google Scholar
  8. 8.
    Clarke SH, Staudt LM, Kavaler J, Schwartz D, Gerhard V, Weigert, MG: V-region gene usage and somatic mutation in the primary and secondary response to influenza virus hemagglutinin. J Immunol 144:2795–2801, 1990Google Scholar
  9. 9.
    Andria ML, Levy S, Benjamini E: Diverse VH and VL genes are used to produce antibodies against a devined protein epitope. J Immunol 144:2614–1629, 1990Google Scholar
  10. 10.
    Alt FW, Yancopoulos GD, Blackwell TK, Wood C, Thomas E, Boss M, Coffman R, Rosenberg N, Tonegawa S, Baltimore D: Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J 3:1209–1219, 1984Google Scholar
  11. 11.
    Alt F, Blackwell K, Yancopoulos G: Development of primary antibody repertoire. Science 238:1079, 1987Google Scholar
  12. 12.
    Siden E, Alt FW, Shinefeld L, Sato V, Baltimore D: Synthesis of immunoglobulin μ chain gene products preceeds synthesis of light chain during B-lymphocyte development. Proc Natl Acad Sci USA 78:1823–1827, 1981Google Scholar
  13. 13.
    Reth M, Petrac E, Wiese P, Lobel L, Alt FW: Activation of VK gene rearrangement in pre-B cell follows the expression of membrane bound immunoglobulin chains. EMBO J 6:3299, 1987Google Scholar
  14. 14.
    Korsmeyer SJ, Hieter PA, Sharrow SO, Goldman CK, Leder P, Waldman T: Normal human B cells display ordered light chain gene rearrangements and deletions. J Exp Med 156:975–985, 1982Google Scholar
  15. 15.
    Yancopoulos GD, Desiderio DV, Paskind M, Kearney JF, Baltimore D, Alt FW. Preferential utilization of the most JH proximal VH gene segments in pre-B cells lines. Nature 311:757–759, 1984Google Scholar
  16. 16.
    Perlmutter RM, Kearney JF, Chang SP, Hood LE: Developmentally controlled expression of immunoglobulin VH genes. Science 127:1597–1600, 1985Google Scholar
  17. 17.
    Griffin JA, Spalding: VH gene expression by nontransformed pre-B cells upon differentiation in vitro. J Immunol 140:3982–3987, 1988Google Scholar
  18. 18.
    Yancopoulos GD, Malynn BA, Alt FA: Developmentally regulated and strain-specific expression of murine VH gene families. J Exp Med 168:417–435, 1988Google Scholar
  19. 19.
    Malynn BA, Yancopoulos GD, Barth JE, Bona CA, Alt FW: Biased expression of JH proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice. J Exp Med 171:843–859, 1990Google Scholar
  20. 20.
    Schroeder HW, Hillson JL, Perlmutter RM: Early restriction of the human antibody repertoire. Science 238:791–793, 1987Google Scholar
  21. 21.
    Malynn BA, Berman JE, Yancopoulos GD, Bona CA, Alt FW: Expression of the immunoglobulin heavy chain variable gene repertoire. Current Topics in Microbiol Immunol 135:75–94, 1987Google Scholar
  22. 22.
    Dildrope R, Krawinklel V, Winter E, Rajewsky K: VK gene expression in murine lipopolysaccharide blasts distribute over nine known VH gene groups and may be random. Eur J Immunol 15:1154–1156, 1985Google Scholar
  23. 23.
    Striebich Ch, Miceli RM, Schulze DH, Kelsoe G, Cerny: Antigen-binding repertoire and IgH chain gene usuage among B cell hybridomas from normal and autoimmune mice. J Immunol 144:1857–1865, 1990Google Scholar
  24. 24.
    Kofler R, Duchosal MA, Dixon J: Complexity, polymorphism, and connectivity of mouse VK gene families. Immunogenetics 29:65–74, 1989Google Scholar
  25. 25.
    Schultz DH, Kelsoe G: Genotypic analysis of B cell colonies by in situ hybridization. Stoichiometric expression of three VH families in adult C57BL/6 and BALB/c mice. J Exp Med 16:163–172, 1987Google Scholar
  26. 26.
    Jeong HD, Teale JM: Comparison of the fetal and adult functional B cell repertoires by analysis of VH gene family expression. J Exp Med 168:589, 1988Google Scholar
  27. 27.
    Boss NA, Meeuwsen: B cell repertoire in adult antigen-free and conventional neonatal BALB/c mice I preferential utilization of CH-proximal VH gene family PC7183. Eur J Immunol 19:1811–1815, 1989Google Scholar
  28. 28.
    Kaushik A, Shulze DH, Bona CA, Kelsoe G: Murine VK gene expression violates the VH paradigm. J Exp Med 169:1859–1864, 1989Google Scholar
  29. 29.
    Teale JM, Morris EG: Comparison of VK gene family expression in adult and fetal B cells. J Immunol 143:2768–2772, 1989Google Scholar
  30. 30.
    Lawler AM, Kearny JF, Kuehl M, Gearhart PJ: Early rearrangements of genes encoding murine immunoglobulin K chains, unlike genes encoding heavy chains, use variable gene segments dispersed throughout the locus. Proc Natl Acad Sci 86:6744–6747, 1989Google Scholar
  31. 31.
    Kastner DL, McIntyre TM, Mallett CP, Harman AB, Steinberg AD: Direct quantitative in situ hybridization studies of Ig VH utilization. J Immunol 143:2761–2767, 1989Google Scholar
  32. 32.
    Holmberg D: High connectivity of natural antibodies, perferentially use 7183 and QUPC52 families. Eur J Immunol 17:399–405, 1987Google Scholar
  33. 33.
    Bellon B, Manheimer-Lory A, Monestier M, Moran T, Dimitriu-Bona A, Alt F, Bona C: High frequency of auto-antibodies bearing crossreactive idiotopes among hybridomas using VH 7183 genes prepared from normal and autoimmune strains. J Clin Invest 79:1044–1053, 1987Google Scholar
  34. 34.
    Logtenberg T, Young FM, VanEs JH, Gmeling-Meyling FHJ, Alt FW: Autoantibodies encoded by the most JH proximal human immunoglobulin heavy chain variable region gene. J Exp Med 170:1347–1355, 1989Google Scholar
  35. 35.
    Berman JE, Mellis SJ, Pollock R, Smith CL, Suh H, Heinke B, Kowal C, Surti U, Chess L, Cantor CR, Alt FW: Content and organization of the human Ig VH locus: Definition of three new VH families and linkage to the Ig CH locus. EMBO J 7:727, 1988Google Scholar
  36. 36.
    Manheimer-Lory AJ, Monestier M, Bellon B, Alt FW, Bona CA: Fine specificity, idiotypy and nature of cloned heavy chain variable region genes of murine monoclonal rheumatoid factor antibodies. Proc Natl Acad Sci USA 83:8293–8297, 1986Google Scholar
  37. 37.
    Monestier M, Bonin B, Migliorini P, Dang H, Datt S, Kuppers R, Rose N, Maurer P, Talal N, Bona C: Autoantibodies of various specificities encoded by genes from the VHJ558 family bind to foreign antigens and share idiotopes of antibodies specific for self and foreign antigens. J Exp Med 166:1109–1124, 1987Google Scholar
  38. 38.
    Monestier M, Manheimer-Lory A, Bellon B, Painter C, Dang H, Talal N, Zanetti M, Schwartz R, Pisetsky D, Kuppers R, Rose N, Brochier J, Klareskog L, Holmdahl R, Erlanger B, Alt F, Bona C: Shared idiotopes and restricted VH genes characterize murine autoantibodies of various specificities. J Clin Invest 78:753–759, 1986Google Scholar
  39. 39.
    Bailey NC, Fidanza V, Mayer R, Mazza G, Fougereau M, and Bona C: Activation of clones producing self reactive antibodies by foreign antigens and anti-idiotype antibody carrying the internal image of the antigen. J Clin Invest 84:744–756, 1989Google Scholar
  40. 40.
    Monier JC, Brochier J, Moreira A, Sault C, Roux B: Generation of hybridoma antibodies to double-stranded DNA from nonautoimmune BALB/c strain: Studies on anti-idiotypes. Immunol Lett 8:61–68, 1984Google Scholar
  41. 41.
    Homdahl R, Bailey C, Enander I, Mayer R, Klareskog L, Moran T, Bona C: Origin of the autoreactive anti-type II collagen response II. Specificities, antibody isotypes and usuage of V-gene families of anti-type II collagen B cells. J Immunol 142:1881–1886, 1989Google Scholar
  42. 42.
    Painter CJ, Monestier M, Chew A, Bona-Dimitriu A, Kasturi K, Bailey C, Scott V, Sidman ChL: Autoantibodies from viable motheaten mice. J Exp Med 167:1137–1153, 1988Google Scholar
  43. 43.
    Monestier M, Bona CA: Antibodies possessing multiple antigen specificities and exhibiting extensive idiotypic cross-reactivity. Int Rev Immunol 3:59–71, 1988Google Scholar
  44. 44.
    Fidanza V, Mayer R, Zaghouani H, Diliberti MA, Bona CA: Autoantibodies Ly1 and immunoglobulin V gene expression in hybridomas obtained from young and from old New Zealand black mice. Arth Rheum 33:711–723, 1990Google Scholar
  45. 45.
    Kasturi K, Monestier M, Mayer R, Bona C: Biased usage of certain VK gene families by autoantibodies and their polymorphism in autoimmune strains. Mol Immunol 25:214–219, 1988Google Scholar
  46. 46.
    Bailey NC, Blackwell TK, Alt FW, Bona CA: Complexity of the immunoglobulin light chain VK1 gene family in the New Zealand black mouse (submitted for publication)Google Scholar
  47. 47.
    Snedecor GW, Cochran WG: Statistical Methods, 6th ed. Ames, Iowa State University Press, 1967, pp 228–253Google Scholar
  48. 48.
    Reininger L, Ollier P, Kaushik A, Jatton JC: Novel V genes encode virtually identical variable regions of six murine monoclonal anti-bromelain-treated red blood cell auto-antibodies. J Immunol 138:316–323, 1987Google Scholar
  49. 49.
    Kaushik A, Schultze DH, Bonilla FA, Bona C, Kelsoe G: Stochastic pairing of VH and VK families occurs in polyclonally activated B cells. Proc Natl Acad Sci 87:4932–4936, 1990Google Scholar
  50. 50.
    Schlomchik MJ, Marshak-Rothstein A, Wolfowicz, Rothstein TL, Weigert MG: The role of clonal selection and somatic mutation in autoimmunity. Nature 328:805–811, 1987Google Scholar
  51. 51.
    Kasturi KN, Mayer R, Bona CA, Scott WT, Sidman CL: Structure of V-genes encoding autoantibodies specific for thymocytes and red blood cells in meV mice. J Immunol (in press)Google Scholar
  52. 52.
    Herzenberg LA, Stall AM, Labor PA, Sidman Ch, Moore WA, Parks DR, Herzenberg LA: The Ly1B cell lineage. Immunol Rev 93:81–102, 1986Google Scholar
  53. 53.
    Hayakawa K, Hardy RR, Parks DR, Herzenberg LA: The Ly1 B cell subpopulation in normal, immunodefective and autoimmune mice. J Exp Med 157:202–218, 1983Google Scholar
  54. 54.
    Sidman CL, Shultz LD, Hardy RR, Hayakawa K, Hertzenberg LA: Production of Immunoglobulin isotypes by Ly-1 + B cells in viable motheaten and normal mice. Science 232:1423–1425, 1986Google Scholar
  55. 55.
    Hayakawa K, Hardy RR, Herzenberg LA, Herzenberg LA: Progenitors for Ly1 B cells are distinct from the progenitors of other B cells. J Exp Med 161:1554–1568, 1985Google Scholar
  56. 56.
    Haughton GL, Arnold W, Bishop GA, Merculino TJ: The CH-series of murine B cell lymphomas: Neoplastic analogens of Ly1 normal V cells. Immunol Rev 93:35–47, 1986Google Scholar
  57. 57.
    Pennell CA, Arnold LW, Houghton G, Clarke SH: Restricted variable region gene expression among Ly-1 + B cell lymphomas. J Immunol 141:2788–2796, 1988Google Scholar
  58. 58.
    Forster I, Gu H, Rajewsky K: Germline antibody V-regions as determinants of clonal persistence of malignant growth in the B cell compartment. EMBO J 7:3693–3703, 1988Google Scholar
  59. 59.
    Tarlinton D, Stall AM, Herzenberg LA: Repetitive usuage of immunoglobulin VH and D gene segments in CD5 + Ly1-B clones of (NZB×NZW) F1 mice. EMBO J 7:3705–3710, 1988Google Scholar
  60. 60.
    Conger JD, Sage JJ, Corley RB: Diversity in the available repertoire of murine antibodies rective with bromelaintreated isologous erythrocytes. J Immunol 143:4044–4052, 1989Google Scholar
  61. 61.
    Mayer R, Zaghouani H, Kaushik A, Kasturi K, Fidanza V, Bona CA: The expression of Ly-1 and immunoglobulin variable gene families in hybridomas producing autoantibodies of various specificities.In The Molecular Aspects of Autoimmunity, N Farid, C Bona (eds). New York, Academic Press, 1990, pp 1–27Google Scholar
  62. 62.
    Mayer R, Zaghouani H, Usuba O, Bona CA: The Ly1 gene expression in murine hybridomas producing autoantibodies. Autoimmunity 6:293–305, 1990Google Scholar
  63. 63.
    Dighiero G, Lymberi P, Holmberg D, Ludquist I, Coutinho A, Avrameas S: High frequency of natural autoantibodies in normal newborn mice. J Immunol 134:765–771, 1985Google Scholar
  64. 64.
    Bonilla FA, Zaghouani H, Rubin M, Bona CA: VK gene usage, idiotype expression and antigen binding among clones expressing the VHX24 gene family derived from naive and antiidiotype immune BALB/c mice. J Immunol 145:616–622, 1990Google Scholar
  65. 65.
    Pennell ChrA, Mercolino ThJ, Grdina TA, Arnold LW, Haughton G, Clarke SH: Biased immunoglobulin variable region gene expression by Ly-1 B cells due to clonal selection. Eur J Immunol 19:1283–1295, 1989Google Scholar
  66. 66.
    Reininger L, Shikata T, Ozaki S, Shirai T, Jatton JC, Izni S: Variable region sequences of pathogenic anti-mouse red blood cell autoantibodies from autoimmune NZB mice. Eur J Immunol 20:771–777, 1990Google Scholar
  67. 67.
    Schlomchik M, Nemazee D, van Snick J, Weigert M: Variable region sequences of murine IgM and IgM monoclonal autoantibodies (rheumatoid region sequences of murine IgM and IgM monoclonal autoantibodies (rheumatoid factors). 11. Comparison of hybridomas derived by lipopolysac-charide stimulation and secondary protein immunization. J Exp Med 165:970–988, 1987Google Scholar

Copyright information

© Plenum Publishing Corporation 1990

Authors and Affiliations

  • Constantin A. Bona
    • 1
  • Yukiko Saitoh
    • 1
  • Garnett Kelson
    • 2
  1. 1.Department of MicrobiologyMount Sinai School of MedicineNew York
  2. 2.Department of Microbiology and ImmunologyThe University of Maryland School of MedicineBaltimore

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