Serum-mediated suppression of nonspecific B cell activation. II. Relative resistance of B cells from the NZB mouse strain to regulation by a natural inhibitor in normal mouse serum.

Recent work has shown that normal mouse serum (NMS) and plasma contain inhibitory substance(s), termed NMS-In, that suppress proliferative and polyclonal antibody responses elicited in vitro with various B cell mitogens. In this study, the NZB mouse, which has a high degree of spontaneous polyclonal B cell activity, was examined for possible reduced amounts of NMS-In. Also, the capacity of NZB B cells to be inhibited by NMS-In was determined. It was found that sera from NZB mice had normal amounts of NMS-In, as assessed by inhibition of mitogenesis of spleen cells in culture induced by bacterial endotoxin (ET). However, B cells of the NZB mouse were found to be abnormal, requiring approximately 4 to 7 times more NMS-In to inhibit polyclonal antibody synthesis and mitogenesis elicited by ET than B cells of more immunologically normal mice. Removal of T cells by treatment with anti-thy 1.2 and complement did not change the sensitivity of the NZB B cells to NMS-In. Insensitivity to NMS-In was expressed in B cells from relatively young NZB mice, e.g., 9 to 15 wk of age. The relative resistance of B cells of the NZB mouse to regulation by a natural inhibitor in NMS could partially serve to explain their high level of spontaneous antibody synthesis. Furthermore, the fact that B cells of the NZB mouse were ultimately susceptible to inhibition by relatively large amounts of NMS-In affords the opportunity in the future to suppress polyclonal antibody activity in the NZB mouse with purified NMS-In in an attempt to ameliorate autoimmune disease.