B cells are selectively associated with thymic cortical but not medullary pathology in NZB mice.

Abnormal expansion of autoantibody-synthesizing B cells and self-reactive T cells, which most likely escape negative selection within the thymus, have both been characterized and reasoned to play a role in the pathogenesis of autoimmunity in NZB mice. Support for this thesis has been our observation that NZB mice have severe cortical and medullary thymic microarchitectural defects. As a means to dissect the roles of T and B cells in the induction of such abnormalities, B cell-deficient NZB mice were bred by backcrossing the Igh6(null)allele on to the NZB background (NZB-muMT mice). Such mice showed undetectable levels of autoantibodies. NZB-muMT mice, as compared to wild-type NZB mice, had lower absolute numbers of CD4(+)T cells. Furthermore, thymic abnormalities in NZB-muMT mice were restricted to the medulla. These data suggest that, while B cells may play a role in thymic cortical abnormalities, the medullary abnormalities are induced by other mechanisms.