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J Exp Med. 1979 Jul 1; 150(1): 31–43.
PMCID: PMC2185603

CBA/N X-linked B-cell defect prevents NZB B-cell hyperactivity in F1 mice


NZB mice and their F1 hybrids produce excessive polyclonal IgM and autoantibodies of both IgM and IgG classes. CBA/N mice and CBA/N- mothered F1 males fail to make antibody to many T-independent antigens and have low levels of serum IgM; further, these mice lack a population of splenic B cells characterized by a low-to-intermediate density of surface IgM. We have studied male CBA/N, NZB, CBA/N X NZB, NZB X CBA/N, and CBA/J mice; female CBA/N X NZB mice; and males of several control crosses of NZB and CBA/N mice. We have found that the CBA/N X-linked defect of T-independent immune response is completely expressed in CBA/N X NZB mice. In marked contrast to NZB mice and to NZB mice and to NZB F1 hybrids bearing at least one normal X chromosome, the CBA/N X NZB males failed to respond to two T-independent antigens, had small numbers of splenic IgM-producing cells, barely detectable splenic IgM production, and splenic B-cell surface-Ig patterns resembling those of CBA/N mice. These data suggest that the NZB B-cell abnormality resulting in excessive IgM production occurs almost exclusively in that population of B cells affected by the CBA/N X chromome-linked defect. Preliminary studies suggest that CBA/N X chromosome retards the spontaneous development of anti-erythrocyte autoantibodies in CBA/N X NZB males. Castration, known to accelerate autoimmune disease in certain NZB F1 males, appears to have no influence on the immune functions examined in this study.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Howie JB, Helyer BJ. Autoimmune disease in mice. Ann N Y Acad Sci. 1965 Jun 30;124(1):167–177. [PubMed]
  • East J. Immunopathology and neoplasms in New Zealand black (NZB) and SJL-J mice. Prog Exp Tumor Res. 1970;13:84–134. [PubMed]
  • Deheer DH, Edginton TS. Cellular events associated with the immunogenesis of anti-erythrocyte autoantibody responses of NZB mice. Transplant Rev. 1976;31:116–155. [PubMed]
  • Shirai T, Mellors RC. Natural cytotoxic autoantibody against thymocytes in NZB mice. Clin Exp Immunol. 1972 Sep;12(1):133–152. [PMC free article] [PubMed]
  • Raveché ES, Steinberg AD, Klassen LW, Tjio JH. Genetic studies in NZB mice. I. Spontaneous autoantibody production. J Exp Med. 1978 May 1;147(5):1487–1502. [PMC free article] [PubMed]
  • Izui S, McConahey PJ, Dixon FJ. Increased spontaneous polyclonal activation of B lymphocytes in mice with spontaneous autoimmune disease. J Immunol. 1978 Dec;121(6):2213–2219. [PubMed]
  • Moutsopoulos HM, Boehm-Truitt M, Kassan SS, Chused TM. 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]
  • Bourgois A, Kitajima K, Hunter IR, Askonas BA. Surface immunoglobulins of lipopolysaccharide-stimulated spleen cells. The behavior of IgM, IgD and IgG. Eur J Immunol. 1977 Mar;7(3):151–153. [PubMed]
  • Evans MM, Williamson WG, Irvine WJ. The appearance of immunological competence at an early age in New Zealand black mice. Clin Exp Immunol. 1968 Jun;3(5):375–383. [PMC free article] [PubMed]
  • Playfair JH. Strain differences in the immune response of mice. I. The neonatal response to sheep red cells. Immunology. 1968 Jul;15(1):35–50. [PMC free article] [PubMed]
  • Staples PJ, Steinberg AD, Talal N. Induction of immunologic tolerance in older New Zealand mice repopulated with young spleen, bone marrow, or thymus. J Exp Med. 1970 Jun 1;131(6):1223–1238. [PMC free article] [PubMed]
  • Playfair JH. 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]
  • de Vries MJ, Hijmans W. A deficient development of the thymic epithelium and auto-immune disease in NZB mice. J Pathol Bacteriol. 1966 Apr;91(2):487–494. [PubMed]
  • de Vries MJ, Hijmans W. Pathological changes of thymic epithelial cells and autoimmune disease in NZB, NZW and (NZB x NZW)F1 mice. Immunology. 1967 Feb;12(2):179–196. [PMC free article] [PubMed]
  • Cantor H, Asofsky R, Talal N. Synergy among lymphoid cells mediating the graft-versus-host response. I. Synergy in graft-versus-host reactions produced by cells from NZB-Bl mice. J Exp Med. 1970 Feb;131(2):223–234. [PMC free article] [PubMed]
  • Gelfand MC, Steinberg AD. Mechanism of allograft rejection in New Zealand mice. I. Cell synergy and its age-dependent loss. J Immunol. 1973 Jun;110(6):1652–1662. [PubMed]
  • Barthold DR, Kysela S, Steinberg AD. Decline in suppressor T cell function with age in female NZB mice. J Immunol. 1974 Jan;112(1):9–16. [PubMed]
  • Cantor H, McVay-Boudreau L, Hugenberger J, Naidorf K, Shen FW, Gershon RK. Immunoregulatory circuits among T-cell sets. II. Physiologic role of feedback inhibition in vivo: absence in NZB mice. J Exp Med. 1978 Apr 1;147(4):1116–1125. [PMC free article] [PubMed]
  • Denman AM, Russell AS, Denman EJ. Adoptive transfer of the diseases of New Zealand black mice to normal mouse strains. Clin Exp Immunol. 1969 Dec;5(6):567–595. [PMC free article] [PubMed]
  • DeHeer DH, Edgington TS. 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]
  • Scher I, Frantz MM, Steinberg AD. 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]
  • Cohen PL, Scher I, Mosier DE. In vitro studies of the genetically determined unresponsiveness to thymus-independent antigens in CBA/N mice. J Immunol. 1976 Feb;116(2):301–304. [PubMed]
  • Amsbaugh DF, Hansen CT, Prescott B, Stashak PW, Asofsky R, Baker PJ. Genetic control of the antibody response to type 3 pneumococcal polysaccharide in mice. II. Relationship between IgM immunoglobulin levels and the ability to give an IgM antibody response. J Exp Med. 1974 Jun 1;139(6):1499–1512. [PMC free article] [PubMed]
  • Scher I, Ahmed A, Strong DM, Steinberg AD, Paul WE. X-linked B-lymphocyte immune defect in CBA/HN mice. I. Studies of the function and composition of spleen cells. J Exp Med. 1975 Apr 1;141(4):788–803. [PMC free article] [PubMed]
  • Scher I, Sharrow SO, Paul WE. 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. [PMC free article] [PubMed]
  • Scher I, Steinberg AD, Berning AK, Paul WE. 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. [PMC free article] [PubMed]
  • Raveche ES, Klassen LW, Steinberg AD. Sex differences in formation of anti-T-cell antibodies. Nature. 1976 Sep 30;263(5576):415–416. [PubMed]
  • Roubinian JR, Talal N, Greenspan JS, Goodman JR, Siiteri PK. Effect of castration and sex hormone treatment on survival, anti-nucleic acid antibodies, and glomerulonephritis in NZB/NZW F1 mice. J Exp Med. 1978 Jun 1;147(6):1568–1583. [PMC free article] [PubMed]
  • Melez KA, Reeves JP, Steinberg AD. Modification of murine lupus by sex hormones. Ann Immunol (Paris) 1978 Jul-Sep;129 100(5):707–714. [PubMed]
  • Melez KA, Reeves JP, Steinberg AD. Regulation of the expression of autoimmunity in NZB x NZW F1 mice by sex hormones. J Immunopharmacol. 1978 1979;1(1):27–42. [PubMed]
  • Molinaro GA, Dray S. Antibody coated erythrocytes as a manifold probe for antigens. Nature. 1974 Apr 5;248(448):515–517. [PubMed]
  • Cunningham AJ, Szenberg A. Further improvements in the plaque technique for detecting single antibody-forming cells. Immunology. 1968 Apr;14(4):599–600. [PMC free article] [PubMed]
  • Parker LM, Steinberg AD. The antibody response to polyinosinic polycytidylic acid. J Immunol. 1973 Mar;110(3):742–751. [PubMed]
  • Parker LM, Chused TM, Steinberg AD. Immunofluorescence studies on thymocytotoxic antibody from New Zealand Black mice. J Immunol. 1974 Jan;112(1):285–292. [PubMed]
  • Warner NL. Genetic control of spontaneous and induced antierythrocyte autoantibody production in mice. Clin Immunol Immunopathol. 1973 Apr;1(3):353–363. [PubMed]

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