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. 1981 Feb 1;153(2):221–234. doi: 10.1084/jem.153.2.221

T cell abnormalities in NZB mice occur independently of autoantibody production

PMCID: PMC2186070  PMID: 6453918

Abstract

By means of a series of crosses and backcrosses, ZB.CBA/N mice were prepared bearing largely NZB autosomal genes, but having X chromosomes derived only from CBA/N mice. The CBA/N X chromosome carries a gene, xid, that is associated with the lack of a B cell subset necessary for most of the spontaneous autoantibody production by NZB mice. These ZB.CBA/N mice failed to develop autoantibodies to T cells, erythrocytes, or DNA. The availability of mice that were mostly NZB, but which failed to make autoantibodies, especially anti-T cell antibodies, allowed us to study possible T cell regulatory defects in NZB mice in the absence of either antibodies reactive with such T cells or other autoantibodies. We found that such mice had derangements of T cell regulation as did the NZB mice. These observations strongly suggest that the t cell abnormalities of NZB mice are not caused by the B cell hyperactivity of these mice, but rather represent independent defects. Thus, NZB mice appear to have primary defects in both the B cell population and the T cell population. Whether or not these are separate, or derive from a common precursor cell abnormality, remains to be determined.

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Selected References

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  1. Ahmed A., Scher I., Sharrow S. O., Smith A. H., Paul W. E., Sachs D. H., Sell K. W. B-lymphocyte heterogeneity: development and characterization of an alloantiserum which distinguishes B-lymphocyte differentiation alloantigens. J Exp Med. 1977 Jan 1;145(1):101–110. doi: 10.1084/jem.145.1.101. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Allison A. C., Denman A. M., Barnes R. D. Cooperating and controlling functions of thymus-derived lymphocytes in relation to autoimmunity. Lancet. 1971 Jul 17;2(7716):135–140. doi: 10.1016/s0140-6736(71)92306-3. [DOI] [PubMed] [Google Scholar]
  3. Amsbaugh D. F., Hansen C. T., Prescott B., Stashak P. W., Barthold D. R., Baker P. J. Genetic control of the antibody response to type 3 pneumococcal polysaccharide in mice. I. Evidence that an X-linked gene plays a decisive role in determining responsiveness. J Exp Med. 1972 Oct 1;136(4):931–949. doi: 10.1084/jem.136.4.931. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Berning A. K., Eicher E. M., Paul W. E., Scher I. Mapping of the X-linked immune deficiency mutation (xid) of CBA/N mice. J Immunol. 1980 Apr;124(4):1875–1877. [PubMed] [Google Scholar]
  5. Boswell H. S., Sharrow S. O., Singer A. Role of accessory cells in B cell activation. I. Macrophage presentation of TNP-Ficoll: evidence for macrophage-B cell interaction. J Immunol. 1980 Feb;124(2):989–996. [PubMed] [Google Scholar]
  6. Braverman I. M. Study of autoimmune disease in New Zealand mice. I. Genetic features and natural history of NZB, NZY and NZW strains and NZB-NZW hybrids. J Invest Dermatol. 1968 Jun;50(6):483–499. doi: 10.1038/jid.1968.79. [DOI] [PubMed] [Google Scholar]
  7. Burnet M., Holmes M. C. Genetic investigations of autoimmune disease in mice. Nature. 1965 Jul 24;207(995):368–371. doi: 10.1038/207368a0. [DOI] [PubMed] [Google Scholar]
  8. Datta S. K., Schwartz R. S. Genetics of expression of xenotropic virus and autoimmunity in NZB mice. Nature. 1976 Sep 30;263(5576):412–415. doi: 10.1038/263412b0. [DOI] [PubMed] [Google Scholar]
  9. DeHeer D. H., Edgington T. S. Evidence for a B lymphocyte defect underlying the anti-X anti-erythrocyte autoantibody response of NZB mice. J Immunol. 1977 May;118(5):1858–1863. [PubMed] [Google Scholar]
  10. Dixon F. J. The pathogenesis of murine systemic lupus erythematosus. Rous--Whipple Award lecture. Am J Pathol. 1979 Oct;97(1):10–16. [PMC free article] [PubMed] [Google Scholar]
  11. Eisenberg R. A., Theofilopoulos A. N., Andrews B. S., Peters C. J., Thor L., Dixon F. J. Natural thymocytotoxic autoantibodies in autoimmune and normal mice. J Immunol. 1979 Jun;122(6):2272–2278. [PubMed] [Google Scholar]
  12. Fernandes G., Yunis E. J., Good R. A. Age and genetic influence on immunity in NZB and autoimmune-resistant mice. Clin Immunol Immunopathol. 1976 Nov;6(3):318–333. doi: 10.1016/0090-1229(76)90085-4. [DOI] [PubMed] [Google Scholar]
  13. Fournié G. J., Lambert P. H., Bankhurst A. D., Miescher P. A. Features of the immune response to DNA in mice II. Participation of B and T cells. Clin Exp Immunol. 1976 Oct;26(1):52–56. [PMC free article] [PubMed] [Google Scholar]
  14. Ghaffar A., Playfair J. H. The genetic basis of autoimmunity in NZB mice studied by progeny-testing. Clin Exp Immunol. 1971 Mar;8(3):479–490. [PMC free article] [PubMed] [Google Scholar]
  15. Glimcher L. H., Steinberg A. D., House S. B., Green I. The autologous mixed lymphocyte reaction in strains of mice with autoimmune disease. J Immunol. 1980 Oct;125(4):1832–1838. [PubMed] [Google Scholar]
  16. Holmes M. C., Burnet F. M. The characteristics of F1 and backcross hybrids between "high leukaemia" (AKR) and "autoimmune" (NZB) mouse strains. Aust J Exp Biol Med Sci. 1966 Jun;44(3):235–249. doi: 10.1038/icb.1966.24. [DOI] [PubMed] [Google Scholar]
  17. Howie J. B., Helyer B. J. The immunology and pathology of NZB mice. Adv Immunol. 1968;9:215–266. doi: 10.1016/s0065-2776(08)60444-7. [DOI] [PubMed] [Google Scholar]
  18. Huber B., Gershon R. K., Cantor H. Identification of a B-cell surface structure involved in antigen-dependent triggering: absence of this structure on B cells from CBA/N mutant mice. J Exp Med. 1977 Jan 1;145(1):10–20. doi: 10.1084/jem.145.1.10. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Huston D. P., Rich R. R., Steinberg A. D., Truitt G. A. Requlation of cytotoxic lymphocyte responses in New Zealand mice by alloantigen-activated spleen cells. J Immunol. 1979 Apr;122(4):1476–1481. [PubMed] [Google Scholar]
  20. Huston D. P., Steinberg A. D. Animal models of human systemic lupus erythematosus. Yale J Biol Med. 1979 May-Jun;52(3):289–305. [PMC free article] [PubMed] [Google Scholar]
  21. Huston D. P., Steinberg A. D. NZB cytotoxic lymphocyte responses. Kinetic analyses. J Exp Med. 1980 Sep 1;152(3):748–753. doi: 10.1084/jem.152.3.748. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Izui S., McConahey P. J., Dixon F. J. Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol. 1978 Dec;121(6):2213–2219. [PubMed] [Google Scholar]
  23. Janeway C. A., Jr, Barthold D. R. An analysis of the defective response of CBA/N mice to T-dependent antigens. J Immunol. 1975 Oct;115(4):898–900. [PubMed] [Google Scholar]
  24. Klassen L. W., Krakauer R. S., Steinberg A. D. Selective loss of suppressor cell function in New Zealand mice induced by NTA. J Immunol. 1977 Sep;119(3):830–830. [PubMed] [Google Scholar]
  25. Knight J. G., Adams D. D., Purves H. D. The genetic contribution of the NZB mouse to the renal disease of the NZB x NZW hybrid. Clin Exp Immunol. 1977 May;28(2):352–358. [PMC free article] [PubMed] [Google Scholar]
  26. Manny N., Datta S. K., Schwartz R. S. Synthesis of IgM by cells of NZB and SWR mice and their crosses. J Immunol. 1979 Apr;122(4):1220–1227. [PubMed] [Google Scholar]
  27. Mond J. J., Scher I., Mosier D. E., Baese M., Paul W. E. T-independent responses in B cell-defective CBA/N mice to Brucella abortus and to trinitrophenyl (TNP) conjugates of Brucella abortus. Eur J Immunol. 1978 Jul;8(7):459–463. doi: 10.1002/eji.1830080703. [DOI] [PubMed] [Google Scholar]
  28. Morton J. I., Siegel B. V. Transplantation of autoimmune potential. I. Development of antinuclear antibodies in H-2 histocompatible recipients of bone marrow from New Zealand Black mice. Proc Natl Acad Sci U S A. 1974 Jun;71(6):2162–2165. doi: 10.1073/pnas.71.6.2162. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Mosier D. E., Scher I., Paul W. E. In vitro responses of CBA/N mice: spleen cells of mice with an X-linked defect that precludes immune responses to several thymus-independent antigens can respond to TNP-lipopolysaccharide. J Immunol. 1976 Oct;117(4):1363–1369. [PubMed] [Google Scholar]
  30. Moutsopoulos H. M., Boehm-Truitt M., Kassan S. S., Chused T. M. Demonstration of activation of B lymphocytes in New Zealand black mice at birth by an immunoradiometric assay for murine IgM. J Immunol. 1977 Nov;119(5):1639–1644. [PubMed] [Google Scholar]
  31. Nakajima P. B., Datta S. K., Schwartz R. S., Huber B. T. Localization of spontaneously hyperactive B cells of NZB mice to a specific B cell subset. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4613–4616. doi: 10.1073/pnas.76.9.4613. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Ochiai T., Ahmed A., Scher I., Sell K. W., Steinberg A. D. Functional characterization of a naturally occurring antibody cytotoxic for a subpopulation of splenic T cells. Transplantation. 1976 Jul;22(1):1–8. doi: 10.1097/00007890-197607000-00001. [DOI] [PubMed] [Google Scholar]
  33. Parker L. M., Chused T. M., Steinberg A. D. Immunofluorescence studies on thymocytotoxic antibody from New Zealand Black mice. J Immunol. 1974 Jan;112(1):285–292. [PubMed] [Google Scholar]
  34. Parker L. M., Steinberg A. D. The antibody response to polyinosinic polycytidylic acid. J Immunol. 1973 Mar;110(3):742–751. [PubMed] [Google Scholar]
  35. Playfair J. H. Strain differences in the immune responses of mice. 3. A raised tolerance threshold in NZB thymus cells. Immunology. 1971 Dec;21(6):1037–1043. [PMC free article] [PubMed] [Google Scholar]
  36. Quimby F. W., Schwartz R. S. The etiopathogenesis of systemic lupus erythematosus. Pathobiol Annu. 1978;8:35–59. [PubMed] [Google Scholar]
  37. Raveche E. S., Tjio J. H., Steinberg A. D. Genetic studies in NZB mice. III. Induced anti-nucleic acid antibody production. J Immunol. 1979 Apr;122(4):1454–1460. [PubMed] [Google Scholar]
  38. Raveché E. S., Steinberg A. D., Klassen L. W., Tjio J. H. Genetic studies in NZB mice. I. Spontaneous autoantibody production. J Exp Med. 1978 May 1;147(5):1487–1502. doi: 10.1084/jem.147.5.1487. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Raveché E. S., Tjio J. H., Steinberg A. D. Genetic studies in NZB mice. II. Hyperdiploidy in the spleen of NZB mice and their hybrids. Cytogenet Cell Genet. 1979;23(3):182–193. doi: 10.1159/000131324. [DOI] [PubMed] [Google Scholar]
  40. Romain P. L., Cohen P. L., Fish F., Ziff M., Vitetta E. S. The specific B cell subset lacking in the CBA/N mouse is not required for the production of autoantibody in (CBA/N x NZB)F1 male mice. J Immunol. 1980 Jul;125(1):246–251. [PubMed] [Google Scholar]
  41. Scher I., Berning A. K., Asofsky R. X-linked B lymphocyte defect in CBA/N mice. IV. Cellular and environmental influences on the thymus dependent IgG anti-sheep red blood cell response. J Immunol. 1979 Jul;123(1):477–486. [PubMed] [Google Scholar]
  42. Scher I., Frantz M. M., Steinberg A. D. The genetics of the immune response to a synthetic double-stranded RNA in a mutant CBA mouse strain. J Immunol. 1973 May;110(5):1396–1401. [PubMed] [Google Scholar]
  43. Scher I., Sharrow S. O., Paul W. E. X-linked B-lymphocyte defect in CBA/N mice. III. Abnormal development of B-lymphocyte populations defined by their density of surface immunoglobulin. J Exp Med. 1976 Aug 1;144(2):507–518. doi: 10.1084/jem.144.2.507. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Scher I., Steinberg A. D., Berning A. K., Paul W. E. X-linked B-lymphocyte immune defect in CBA/N mice. II. Studies of the mechanisms underlying the immune defect. J Exp Med. 1975 Sep 1;142(3):637–650. doi: 10.1084/jem.142.3.637. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Shirai T., Hayakawa K., Okumura K., Tada T. Differential cytotoxic effect of natural thymocytotoxic autoantibody of NZB mice on functional subsets of T cells. J Immunol. 1978 Jun;120(6):1924–1929. [PubMed] [Google Scholar]
  46. Shirai T., Yoshiki T., Mellors R. C. Age-decrease of cells sensitive to an autoantibody-specific for thymocytes and thymus-dependent lymphocytes in NZB mice. Clin Exp Immunol. 1972 Dec;12(4):455–464. [PMC free article] [PubMed] [Google Scholar]
  47. Shirai T., Yoshiki T., Mellors R. C. Thymus dependence of cells in peripheral lymphoid tissues and in the circulation sensitive to natural thymocytotoxic autoantibody in NZB mice. J Immunol. 1972 Jul;109(1):32–37. [PubMed] [Google Scholar]
  48. Smith J. B., Pasternak R. D. Syngeneic mixed lymphocyte reaction in mice: strain distribution, kinetics, participating cells, and absence in NZB mice. J Immunol. 1978 Nov;121(5):1889–1892. [PubMed] [Google Scholar]
  49. Taurog J. D., Smathers P. A., Steinberg A. D. Evidence for abnormalities in separate lymphocyte populations in NZB mice. J Immunol. 1980 Aug;125(2):485–490. [PubMed] [Google Scholar]
  50. Theofilopoulos A. N., Eisenberg R. A., Bourdon M., Crowell J. S., Jr, Dixon F. J. Distribution of lymphocytes identified by surface markers in murine strains with systemic lupus erythematosus-like syndromes. J Exp Med. 1979 Feb 1;149(2):516–534. doi: 10.1084/jem.149.2.516. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Warner N. L. Genetic control of spontaneous and induced antierythrocyte autoantibody production in mice. Clin Immunol Immunopathol. 1973 Apr;1(3):353–363. doi: 10.1016/0090-1229(73)90052-4. [DOI] [PubMed] [Google Scholar]

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