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Natural Autoantibodies

  • Sylvia K. Chai
  • Liliana Mantovani
  • Marion T. Kasaian
  • Paolo Casali
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 347)

Abstract

It has been recognized for at least half a century that normal individuals display circulating immunoglobulins (Ig) able to bind a variety of foreign antigens, such as bacteria, virus, fungi, as well as self antigens, such as nucleic acids, phospholipids, erythrocytes, serum proteins, cellular components, insulin, and thyroglobulin1–9. Because these antibodies arise independently of known and/or deliberate immunization, they have been termed natural antibodies. In contrast to antigen-induced antibodies, which are mainly IgG and monoreactive, a considerable proportion of natural antibodies are IgM and polyreactive, that is they bind several unrelated antigens with different affinities. Natural polyreactive and monoreactive IgG and IgA also exist7. Natural antibodies are produced mainly by CD5+ B cells, the predominant lymphocytes in the neonatal B cell repertoire10,11. Because of their broad reactivity for a wide variety of microbial components, natural antibodies play a major role in the primary line of defense against infections. Because of their ability to bind self antigens, they may provide the “templates” for the autoantibodies characteristic of autoimmune conditions, particularly those associated with expansion of CD5+ B cells, e.g., rheumatoid arthritis12-14.

Keywords

Systemic Lupus Erythematosus Chronic Lymphocytic Leukemia Cell Repertoire Natural Antibody Soluble Ligand 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    S. Boyden, Natural antibodies and the immune response, Adv. Immunol. 5:1 (1965).CrossRefGoogle Scholar
  2. 2.
    J.G. Michael, Natural antibodies, Curr. Top. Microbiol. Immunol. 48:43 (1969).PubMedGoogle Scholar
  3. 3.
    P. Casali, and A.L. Notkins, CD5+B lymphocytes, polyreactive antibodies and the human B-cell repertoire, Immunol. Today. 10:364 (1989a).CrossRefGoogle Scholar
  4. 4.
    S. Avrameas, Natural autoantibodies: from “horror autotoxicus” to “gnothi seauton”, Immunol. Today. 12:154 (1991).PubMedGoogle Scholar
  5. 5.
    P. Riboldi, M.T. Kasaian, L. Mantovani, H. Ikematsu, and P. Casali, Natural antibodies, in: “Molecular Pathology of Autoimmunity”, C.A. Bona, K. Siminovitch, M. Zanetti, A.N. Theophilopoulos, eds., The Harwood Academic Publishers, New York (1992).Google Scholar
  6. 6.
    M.A. Turman, P. Casali, A.L. Notkins, F.H. Bach, and J.S. Platt, Polyreactive antibodies from CD5+ B cells: antigen specificity and relationship to xenoreactive natural antibodies, Transplantation. 52:710 (1991).PubMedCrossRefGoogle Scholar
  7. 7.
    M.T. Kasaian, H. Ikematsu, and P. Casali, Identification and analysis of a novel human surface CD5- B lymphocyte subset producing natural antibodies, J Immunol. 148:2690 (1992).PubMedGoogle Scholar
  8. 8.
    M.T. Kasaian and P. Casali, Analysis of the human CD5-CD45RAlo B cell subset, Ann NY Acad Sci. 651:59 (1992).PubMedCrossRefGoogle Scholar
  9. 9.
    M. Nakamura S.E. Burastero, A.L. Notkins, and P. Casali, Human monoclonal rheumatoid factor-like antibodies from CD5 (Leu-1+) B cells are polyreactive, J Immunol. 140:4180 (1988).PubMedGoogle Scholar
  10. 10.
    A. Durandy, L. Thuillier, M. Forveille, and A. Fischer, Phenotypic and functional characteristics of human newborns’ B lymphocytes, J.Immunol. 144:60 (1990).PubMedGoogle Scholar
  11. 11.
    N. Gadol, and K.A. Ault, Phenotypic and functional characterization of human Leu 1 (CD5) B cells, Immunol. Rev. 93:23 (1986).PubMedCrossRefGoogle Scholar
  12. 12.
    S.E. Burastero, and P. Casali, Characterization of human CD5 (Leu-1, OKT1)+ B lymphocytes and the antibodies they produce, Contrib Microbiol. Immunol. 11:231 (1989).PubMedGoogle Scholar
  13. 13.
    P. Casali and A.L. Notkins, Probing the human B-cell repertoire with EBV: Polyreactive antibodies and CD5+ B lymphocytes, Ann Rev Immunol. 7:513 (1989).CrossRefGoogle Scholar
  14. 14.
    S.E. Burastero, P. Casali, R.L. Wilder, and A.L. Notkins, Monoreactive high affinity and polyreactive low affinity rheumatoid factors are produced by CD5+ B cells from patients with rheumatoid arthritis, J Exp Med. 168:1979 (1988).PubMedCrossRefGoogle Scholar
  15. 15.
    P. Casali, M.T. Kasaian, and G. Haughton, B-1 (CD5 B) cells, in: “Autoimmunity,” A. Coutinho and M.D. Kazatchkine, ed., John Wiley & Sons, New York (1993). In press.Google Scholar
  16. 16.
    M. Kasaian and P. Casali, Natural antibodies, self recognition and autoimmunityprone B-1 (CD5 B) cells, Autoimmunity. In press (1993).Google Scholar
  17. 17.
    P.L. Schwimmbeck, D.T.Y Yu, and M.B.A. Oldstone, Autoantibodies to HLA B27 in the sera of HLA B27 patients with ankylosing spondylitis and Reiter’s syndrome. Molecular mimicry with Klebsiella Pneumoniae as potential mechanism of autoimmune disease, J. Exp. Med. 166:173 (1987).PubMedCrossRefGoogle Scholar
  18. 18.
    R.B. Rayburne and K.M. Williams, Monoclonal antibodies against and HLA-B27derived peptide reacts with an epitope present on bacterial proteins, J. Immunol. 145:2539 (1990).Google Scholar
  19. 19.
    M.W. Cunningham, J.M. McCormack, P.G. Fenderson, M.K. Ho, E.H. Beachey, and J.B. Dale, Human and murine antibodies cross-reactive with streptococcal M protein and myosin recognize the sequence GLN-LYS-SER-LYS-GLN in M protein, J.Immunol. 143:2677 (1989).PubMedGoogle Scholar
  20. 20.
    E.M. Lafer, J. Rauch, J.R. Andrzejewski, D. Mudd, B. Furie, R.S. Schwartz, D.B. Stollar, Polyspecific monoclonal lupus autoantibodies reactive with both polynucleotides and phospholipids, J. Exp. Med. 153:897 (1981).PubMedCrossRefGoogle Scholar
  21. 21.
    T. Ternynck, S. Avrameas, Murine natural monoclonal autoantibodies: a study of their polyspecificities and their affinities, Immunol. Rev. 94:99 (1986).PubMedCrossRefGoogle Scholar
  22. 22.
    P. Casali, B.S. Prabhakar, and A.L. Notkins, Characterization of multireactive autoantibodies and identification of LEU-1+ B lymphocytes as cells making antibodies binding multiple self and exogenous molecules, Intern. Rev. Immunol. 3:17 (1988).CrossRefGoogle Scholar
  23. 23.
    P.M. Colman, Structure of antibody-antigen complexes: Implications for immune recognition, Adv. Immunol. 43:99 (1988).PubMedCrossRefGoogle Scholar
  24. 24.
    E.A. Kabat, Antibody complementarity and antibody structure, J. Immunol (suppl). 141:S25 (1988).PubMedGoogle Scholar
  25. 25.
    A.G. Amit, R.A. Mariuzza, S.E. Phillips, and R.J. Poliak, Three-dimensional structure of an antigen-antibody complex at 2.8 A resolution, Science. 233:747 (1986).PubMedCrossRefGoogle Scholar
  26. 26.
    R.L. Stanfield, T.M. Fieser, R.A. Lerner, and I.A. Wilson, Crystal structures of an antibody to a peptide and its complex with peptide antigen at 2.8 A, Science 248:712 (1990).PubMedCrossRefGoogle Scholar
  27. 27.
    D. Eilat, D.M. Webster, and A.R. Rees, V region sequences of anti-DNA and anti-RNA autoantibodies from NZB/NZW F1 mice, J. Immunol. 141:1745 (1988).PubMedGoogle Scholar
  28. 28.
    M. Shlomchik, M. Mascelli, H. Shan, M.Z. Radic, D. Pisetsky, A. Marshak-Rothstein, and M. Weigert, Anti-DNA antibodies from autoimmune mice arise by clonal expansion and somatic mutation, J.Exp. Med. 171:265 (1990).PubMedCrossRefGoogle Scholar
  29. 29.
    I. Sanz, P. Casali, J.W. Thomas, A.L. Notkins, and J.D. Capra, Nucleotide sequences of eight human natural antibody VH regions reveals apparent restricted use of VH families, J.Immunol. 142: 4054 (1989a).Google Scholar
  30. 30.
    G.D. Yancopoulos and F. Alt, Developmentally controlled and tissue-specific expression of unrearranged VH gene segments, Cell. 40:271 (1985).PubMedCrossRefGoogle Scholar
  31. 31.
    M. Nakamura, S.E. Burastero, Y. Ueki, J.W. Larrick, A.L. Notkins, P. Casali, Probing the normal and autoimmune B cell repertoire with Epstein-Barr virus. Frequency of B cells producing monoreactive high affinity autoantibodies in patients with Hashimoto’s disease and systemic lupus erythematosus, J Immunol. 141:4165 (1988).PubMedGoogle Scholar
  32. 32.
    Y. Ueki, I. Goldfarb, N. Harindranath, M. Gore, H. Koprowski, A.L. Notkins, A.L., and P. Casali, Clonal analysis of a human antibody response. Quantitation of precursors of antibody-producing cells and generation and characterization of monoclonal IgM, IgG and IgA to rabies virus, J.Exp.Med. 171: 19 (1990).PubMedCrossRefGoogle Scholar
  33. 33.
    H. Ikematsu, M.T. Kasaian, E.W. Schettino, T.H. Steger, P. Casali, Antigen-selected somatic mutations in the VH regions of natural polyreactive human IgG autoantibodies, In preparation (1992).Google Scholar
  34. 34.
    M.T. Kasaian, H. Ikematsu, J.E. Balow, and P. Casali, Cellular origin and VH genes of monoreactive and polyreactive IgA and IgG autoantibodies to DNA in patients wtih systemic lupus erythematosus, In preparation (1992).Google Scholar
  35. 35.
    J. Foote, and C. Milstein, Kinetic maturation of an immune response, Nature 352:530 (1991).PubMedCrossRefGoogle Scholar
  36. 36.
    N. Harindranath, I.S. Goldfarb, H. Ikematsu, S.E. Burastero, R.L. Wilder, A.L. Notkins, and P. Casali, Complete sequence of the genes encoding the VH and VL regions of low and high affinity monoclonal IgM and IgA1 rheumatoid factors produced by CD5+ B cells from a rheumatoid arthritis patient, Int. Immunol. 3:865 (1991).PubMedCrossRefGoogle Scholar
  37. 37.
    H. Ikematsu, N. Harindranath, and P. Casali, Somatic mutations in the VH genes of high affinity antibodies to self and foreign antigens produced by human CD5+ and CD5- B cells, Ann.NY Acad.Sci. 651:319 (1992).PubMedCrossRefGoogle Scholar
  38. 38.
    R.C. Williams Jr., C.C. Malone, and P. Casali, Heteroclitic polyclonal and monoclonal anti-Gm(a) and anti-Gm(g) rheumatoid factors react with epitopes induced in Gm (a-), Gm(g-) IgG by interaction with antigen or by nonspecific aggregation, A possible mechanism for the in vivo generation of rheumatoid factors, J Jmmunol. 149:1817 (1992).Google Scholar
  39. 39.
    L. Mantovani, M.T. Kasaian, R.L. Wilder, and P. Casali, Monoreactive high affinity IgM rheumatoid factor autoantibodies are produced by B-1 cells and utilize somatically mutated VH and VL genes, In preparation (1992).Google Scholar
  40. 40.
    K. Hayakawa, R.R. Hardy, M. Honda, L.A. Herzenberg, A.D. Steinberg, and L.A. Herzenberg, Ly-1 B cells: Functionally distinct lymphocytes that secrete IgM autoantibodies, Proc. Nail. Acad. Sci. USA. 81:2494 (1984).CrossRefGoogle Scholar
  41. 41.
    E.G. Engleman, R. Warnke, R.I. Fox, J. Dilley, C.J. Benike, and R. Levy, Studies of a human T lymphocyte antigen recognized by a monoclonal antibody, Proc. Nat. Acad. Sci. USA. 78:1791 (1981).PubMedCrossRefGoogle Scholar
  42. 42.
    H-J.S. Huang, N.H. Jones, J.L. Strominger, and L.A. Herzenberg, Molecular cloning of Ly-1, a membrane glycoprotein of mouse T lymphocytes and a subset of B cells: Molecular homology to its human counterpart Leu-1/T1 (CD5), Proc. Nat. Acad. Sci. USA. 84:204 (1987).PubMedCrossRefGoogle Scholar
  43. 43.
    N.H. Jones, M.L. Clabby, D.P. Dialynas, H-J.S. Huang, L.A. Herzenberg, and J.L. Strominger, Isolation of complementary DNA clones encoding the human lymphocyte glycoprotein Tl/Leu-1. Nature. 323:346 (1986).PubMedCrossRefGoogle Scholar
  44. 44.
    L.A. Herzenberg, A.M. Stall, P.A. Lalor, C. Sidman, W.A. Moore, D.R. Parks, and L.A. Herzenberg, The LY-1 B cell lineage. Immunol. Rev. 93:81 (1986).PubMedCrossRefGoogle Scholar
  45. 45.
    P.A. Lalor, L.A. Herzenberg, S. Adams, A.M. Stall, A.M., Feedback regulation of murine Ly-1 B cell development, Eur. J. Immunol. 19:507 (1989).PubMedCrossRefGoogle Scholar
  46. 46.
    K. Hayakawa, and R.R. Hardy, Normal, autoimmune, and malignant CD5+B cells: The Ly-1 B lineage?, Ann. Rev. Immunol. 6:197 (1988).CrossRefGoogle Scholar
  47. 47.
    L. Boumsell, A. Bernard, V. Lepage, L. Degos, J. Lemerle, J. Dausset, Some chronic lymphocytic leukemia cells bearing surface immunoglobulins share determinants with T cells, Eur. J. Immunol. 8:900 (1978).PubMedCrossRefGoogle Scholar
  48. 48.
    I. Royston, J.A. Majoa, S.M. Baird, G.L. Meserve, J.C. Griffiths, Human T-cell antigens defined by monoclonal antibodies: The 65,000-dalton antigen of T cells (T65) is also found on chronic lymphocytic leukemia cells bearing surface immunoglobulin, J. Immunol. 125:725 (1980).PubMedGoogle Scholar
  49. 49.
    L. Boumsell, H. Coppin, D. Pham, B. Raynal, J. Lemerle, J. Dausset, and A. Bernard, An antigen shared by human T cell subsets and B cell chronic lymphocytic leukemic cells: Distribution on normal and malignant cells, J. Exp. Med. 152:229 (1988).CrossRefGoogle Scholar
  50. 50.
    F. Caligaris-Cappio, M. Gobbi, M. Bofill, and G. Janossy, Infrequent normal B lymphocytes express features of B-chronic lymphocytic leukemia, J. Exp. Med. 155:623 (1982).PubMedCrossRefGoogle Scholar
  51. 51.
    M. Gobbi, F. Caligaris-Cappio, and G. Janossy, Normal equivalent of cells of B cell malignancies: Analysis with monoclonal antibodies, Brit. J. Haematol. 54:393 (1983).CrossRefGoogle Scholar
  52. 52.
    N. Gadol, and K.A. Ault, Phenotypic and functional characterization of human Leu 1 (CD5) B cells, Immunol. Rev. 93:23 (1986).PubMedCrossRefGoogle Scholar
  53. 53.
    J.H. Antin, S.G. Emerson, P. Martin, N. Gadol, K.A. Ault, LEU-1+ (CD5+)B cells: A major lymphoid subpopulation in human fetal spleen: Phenotypic and functional studies, J. Immunol. 136:505 (1986).PubMedGoogle Scholar
  54. 54.
    K. Hayakawa, R.R Hardy, and L.A. Herzenberg, Peritoneal Ly-1 B cells: Genetic control, autoantibody production, increased lambda light chain expression, Eur. J. Immunol. 16:450 (1986).PubMedCrossRefGoogle Scholar
  55. 55.
    T.J. Kipps, S. Fong, E. Tomhave, P.P. Chen, R.D. Goldfien, and D.A. Carson, High frequency expression of a conserved kappa variable region gene in chronic lymphocytic leukemia, Proc. Natl. Acad. Sci. USA. 84:2916 (1987).PubMedCrossRefGoogle Scholar
  56. 56.
    P. Casali, S.E. Burastero, M. Nakamura, G. Inghirami, A.L. Notkins, Human lymphocytes making rheumatoid factor and antibody to ssDNA belong to the Leu-1+ B-cell subset, Science. 236:77 (1987).PubMedCrossRefGoogle Scholar
  57. 57.
    K. Hayakawa, R.R. Hardy, D.R. Parks, and L.A. Herzenberg, The “Ly-1 B” cell subpopulation in normal, immunodefective, and autoimmune mice, J. Exp. Med. 157:202 (1983).PubMedCrossRefGoogle Scholar
  58. 58.
    P. Casali, S.E. Burastero, J.E. Balow, and A.L. Notkins, High affinity antibodies to ssDNA are produced by CD5-B cells in systemic lupus erythematosus patients, J. Immunol. 143:3476 (1989).PubMedGoogle Scholar
  59. 59.
    K. Hasegawa, H. Nishimura, S. Ogawa, S. Hirose, H. Sato, and T. Shirai, Monoclonal antibodies to epitope of CD45R(B220) inhibit interleukin 4-mediated B cell proliferation and differentiation, Internat. Immunol. 2:367 (1990).CrossRefGoogle Scholar
  60. 60.
    R.S. Mittler, R.S. Greenfield, B.Z. Schacter, N.F. Richard, and M.K. Hoffmann, Antibodies to the leukocyte antigen (T200) inhibit an early phase in the activation of resting human B cells, J. Immunol. 138:3159 (1987).PubMedGoogle Scholar
  61. 61.
    H. Yakura, F.W. Shen, E. Bourcet, and E.A. Boyse, On the function of Ly-5 in the generation of antigen-driven B cell differentiation. Comparison and contrast with Lyb-2, J. Exp. Med. 157:1077 (1983).PubMedCrossRefGoogle Scholar
  62. 62.
    H. Yakura, I. Kawabata, T. Ashida, and M. Katagiri, Differential regulation by Ly-5 and Lyb-2 of IgG production induced by lipopolysaccharide and B cell stimulatory factor-1 (IL-4), J. Immunol. 141:875 (1988).PubMedGoogle Scholar
  63. 63.
    H. Yakura, I. Kawabata, F.W. Shen, and M. Katagiri, Selective inhibition of lipopolysaccharide-induced polyclonal IgG response by monoclonal Ly-5 antibody, J. Immunol. 136:2729 (1986).PubMedGoogle Scholar
  64. 64.
    A. Kantor, A new nomenclature for B cells, Immunol. Today. 12:388 (1991).PubMedCrossRefGoogle Scholar
  65. 65.
    T.J. Kipps, and J.H. Vaughn, Genetic influence on the levels of circulating CD5 B lymphocytes, J. Immunol. 139:1060 (1987).PubMedGoogle Scholar
  66. 66.
    D.M. Klinman, and K.L. Holmes, Differences in the repertoire expressed by peritoneal and splenic Ly-1 (CD5)+B cells, J. Immunol. 144:4520 (1990).PubMedGoogle Scholar
  67. 67.
    G.D. Yancopoulos, S.V. Desiderio, M. Paskind, J.F. Kearney, D. Baltimore, and F.W. Alt, Preferential utilization of the most JH proximal VH segments in pre-B cell lines, Nature. 311:727 (1984).PubMedCrossRefGoogle Scholar
  68. 68.
    M.G. Reth, S. Jackson, and F.W. Alt, VHDJH formation and D-JH replacement during pre-B differentiation: Non-random usage of gene segments, EMBO J. 5:2131 (1986).PubMedGoogle Scholar
  69. 69.
    H.D. Jeong, and J.M. Teale, Comparison of the fetal and adult functional B cell repertoires by analysis of VH gene family expression, J. Exp. Med. 168:589 (1988).PubMedCrossRefGoogle Scholar
  70. 70.
    H.D. Jeong, and J.M. Teale, VH gene repertoire of resting B cells. Preferential use of D-proximal families early in development may be due to distinct B cell subsets, J. Immunol. 143:2752 (1989).PubMedGoogle Scholar
  71. 71.
    B.A. Malynn, G.D. Yancopoulos, J.E. Barth, C.A. Bona, and F.W. Alt, Biased expression of JH-proximal VH genes occurs in the newly generated repertoire of neonatal and adult mice, J. Exp. Med. 171:843 (1990).PubMedCrossRefGoogle Scholar
  72. 72.
    R.M. Perlmutter, J.F. Kearney, S.P. Chang, L.E. Hood, Developmentally controlled expression of immunoglobulin VH genes, Science. 227:1597 (1985).PubMedCrossRefGoogle Scholar
  73. 73.
    P. Brodeur, G.E. Osman, J.J. Mackle, and T.M. Lalor, The organization of the mouse Igh-v locus: Dispersion, interdispersion, and the evaluation of VH gene family clusters, J. Exp. Med. 168:2261 (1988).PubMedCrossRefGoogle Scholar
  74. 74.
    H.W. Schroeder Jr, J.L. Hillson, and R.M. Perlmutter, Early restriction of the human antibody repertoire, Science. 238:791(1987).Google Scholar
  75. 75.
    A.M. Cuisinier, V. Guigou, L. Boubli, M. Fougereau, and C. Tonnelle, Preferential expression of VH5 and VH6 immunoglobulin genes in early human B cell ontogeny, Scand. J. Immunol. 30:493 (1989).PubMedCrossRefGoogle Scholar
  76. 76.
    P.P. Chen, R.W. Soto-Gil, and D.A. Carson, The early expression of some human autoantibody-associated heavy chain variable region genes is controlled by specific regulatory elements, Scand. J. Immunol. 31:673 (1990).PubMedCrossRefGoogle Scholar
  77. 77.
    L.A. Herzenberg, and A.M. Stall, Conventional and Ly-1 B-cell lineages in normal and µ transgenic mice, Cold Spring Harbor Sym. Quant. Biol. 54:219 (1989).CrossRefGoogle Scholar
  78. 78.
    M. Dauphinee, Z. Tovar, and N. Talal, B cells expressing CD5 are increased in Sjogren’s syndrome, Arthritis Rheum. 31:642 (1988).PubMedCrossRefGoogle Scholar
  79. 79.
    M.C. Velasquillo, J. Alcocer-Varela, D. Alarcon-Segovia, J. Cabiedes, and J. Sanchez-Guerrero, Some patients with primary antiphospholipid syndrome have increased circulating CD5+ B cells that correlate with levels of IgM antiphospholipid, Clin.. Expl. Rheum. 9:1 (1991).Google Scholar
  80. 80.
    N. Suzuki, T. Sakane, E.G. Engleman, Anti-DNA antibody production by CD5+ and CD5- B cells of patients with systemic lupus erythematosus, J Clin Invest. 85:238 (1990).PubMedCrossRefGoogle Scholar
  81. 81.
    A. Mannheimer-Lory, J.B. Katz, M. Pillinger, C. Ghossein, A. Smith, and B. Diamond, Molecular characteristics of antibodies bearing an anti-DNAassociated idiotype, J. Exp. Med. 174:1639 (1991).CrossRefGoogle Scholar
  82. 82.
    H. Dersimonian, R.S. Schwartz, K.J. Barrett, D.B. Stollar, Relationship of human variable region heavy chain germline genes to genes encoding anti-DNA autoantibodies, J.lmmunol. 139:2496 (1987).Google Scholar
  83. 83.
    J.H. Van Es, F.H.J. Gmelig-Meyling, W.R.M. Van De Akker, H. Aanstoot, R.H.W.M. Derksen, and T. Logtenberg, Somatic mutations in the variable regions of a human IgG anti-double-stranded DNA autoantibody suggest a role for antigen in the induction of systmic lupus erythematosus, J.Exp. Med. 173: 461 (1991).PubMedCrossRefGoogle Scholar
  84. 84.
    B. Diamond, J.B. Katz, E. Paul, C. Aranow, D. Lustgarten, and M.D. Scharff, The role of somatic mutation in the pathogenic anti-DNA response, Ann. Rev Immunol. 10:731 (1992).CrossRefGoogle Scholar
  85. 85.
    T. Mimura, P.F ernstein, and J.B. Winfield, Autoantibodies specific for different isoforms of CD45 in systemic lupus erythmatosis, J Exp. Med. 172:653 (1990).PubMedCrossRefGoogle Scholar
  86. 86.
    S. Tanaka, T. Matsuyama, A.D. Steinberg, S.F. Schlossman, and C. Morimoto, Anti-lymphocyte antibodies against CD4+2H4+ cell populations in patients with systemic lupus erythmatosis, Arth. Rheum. 32:398 (1989).CrossRefGoogle Scholar
  87. 87.
    N.A. Bos, H. Kimura, C.G. Meewsen, H.De Visser, M.P. Hazenberg, B.S. Wostmann, J.R. Pleasants, R. Benner, and D.M. Marcus, Serum immunoglobulin levels and naturally occuring antibodies against carbohydrate antigens in germ-free BALB/c mice fed chemically defined ultrafiltered diet, Eur.J. Immunol. 19:2335 (1989).PubMedCrossRefGoogle Scholar
  88. 88.
    J.R. Underwood, J.S. Pederson, P.J. Chalmers, and B.H. Toh Hybrids from normal, germ-free, nude and neonatal mice produce monoclonal autoantibodies to eight different intracellular structures, Ciln.Exp.Immunol. 60:417 (1985).Google Scholar
  89. 89.
    R.L. Geller, F.H. Bach, M.A. Turman, P. Casali, and J.L. Platt, Natural antibodies bearing a “polyreactive” idiotype are deposited in rejected discordant xenografts, Transplantation. In press (1992).Google Scholar

Copyright information

© Springer Science+Business Media New York 1994

Authors and Affiliations

  • Sylvia K. Chai
    • 1
  • Liliana Mantovani
    • 1
  • Marion T. Kasaian
    • 1
    • 2
  • Paolo Casali
    • 1
  1. 1.The Department of Pathology and Kaplan Comprehensive Cancer CenterNew York University School of MedicineNew YorkUSA
  2. 2.Immulogic Pharmaceutical CorporationCambridgeUSA

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