Influence of the sex-linked defect in CBA/N mice on autoimmune responses to isologous erythrocytes. Ability to overcome the defect with age.

Normal mice spontaneously develop plaque-forming cells (PFC) specific for antigens on modified self erythrocytes (bromelain-treated mouse erythrocytes [BrMRBC] antigens). Our study demonstrates that the sex-linked defect that results in the inability of CBA/N mice to respond to several T-independent antigens (TI-2 antigens) also regulates the autoantibody response to BrMRBC antigens. Thus, in CBA/N homozygous mice and male F1 offspring of CBA/N-mothered crosses, e.g., (CBA/N X NZB)F1 males, such PFC are absent. To examine whether specific autoreactive B cells are present in defective mice, the latter were stimulated either nonspecifically with the mitogen LPS or by infection with lethal malaria (17XL Plasmodium yoelii) known to induce anti-BrMRBC PFC specifically. The results indicate that modest antibody responses to self antigens could be induced in young (5- to 7-wk old) defective mice and that these responses increased as a function of age. The data is consistent with the view that the defect in CBA/N mice does not result from an absence of functional anti-BrMRBC B cells but rather from low frequencies of the specific precursors, which can be triggered and expanded with age probably by environmental stimulations.