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

Abstract

NZB mice and their F1 hybrids produce excessive polyclonal Ig[immunoglobulin]M and autoantibodies of both IgM and IgG classes. CBA/N mice and CBA/N-mothered F1 males fail to make antibody to many T[thymus]-independent antigens and have low levels of serum IgM; further, these mice lack a population of splenic B [bone marrow-derived] cells characterized by a low-to-intermediate density of surface IgM. Male CBA/N, NZB, CBA/N .times. NZB, NZB .times. CBA/N and CBA/J mice; female CBA/N .times. NZB mice; and males of several control crosses of NZB and CBA/N mice were studied. The CBA/N X-linked defect of T-independent immune response is completely expressed in CBA/N .times. NZB mice. In marked contrast to NZB mice and to NZB F1 hybrids bearing at least 1 normal chromosome, the CBA/N .times. NZB males failed to respond to 2 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. The NZB B-cell abnormality resulting in excessive IgM production apparently occurs almost exclusively in that population of B cells affected by the CBA/N X-chromosome-linked defect. The CBA/N X chromosome apparently retards the spontaneous development of anti-erythrocyte autoantibodies in CBA/N .times. 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.