Major histocompatibility complex-linked and T cell-dependent selection of antibody repertoires. Quantitation of I-E-related specificities in normal mice.

Autoreactive B cell repertoires with major histocompatibility complex (MHC) class II (I-E)-related specificities were investigated by quantitating frequencies of specific B lymphocyte clonal precursors in unmanipulated normal and athymic BALB/c mice and in I-E-negative, MHC-congenic BALB.B10 mice. Clonal culture supernatants containing anti-I-E antibodies were identified by their selective binding to I-Ek alpha Ed beta-transfected fibroblasts, and those containing anti-anti-I-E antibodies were detected by their selective binding to anti-I-E monoclonal antibodies. Analysis of splenic B lymphocytes from BALB/c mice revealed high frequencies of both specificities in the compartment of large, naturally activated cells, but not among small, resting lymphocytes. The selection of such clones was found to be MHC linked because of their absence in BALB.B10 mice, and T cell dependent because of their reduced frequency in athymic BALB/c mice. The positive selection of V regions representing complementarities and mimicries of self-class II antigens may suggest a set of mechanisms participating in the maintenance of natural tolerance.