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.
D000818:Animals; D001323:Autoantibodies / Q000276:immunology; D001327:Autoimmune Diseases / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D003433:Crosses, Genetic; D004912:Erythrocytes / Q000276:immunology; D005260:Female; D008040:Genetic Linkage; D007074:Immunoglobulin G / Q000276:immunology; D007075:Immunoglobulin M / Q000276:immunology; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA / Q000276:immunology; D008814:Mice, Inbred NZB / Q000276:immunology; D012730:Sex Chromosomes; D014960:X Chromosome
D001323:Autoantibodies; D007074:Immunoglobulin G; D007075:Immunoglobulin M