B-LYMPHOCYTES MAY ESCAPE TOLERANCE BY REVISING THEIR ANTIGEN RECEPTORS

To explore mechanisms that prevent autoreactivity in nonautoimmune mice, endogenous immunoglobulin (Ig) light (L) chains that associate with a transgenic anti-DNA heavy chain were analyzed. The antibodies from splenic B cell hybridomas of such mice did not bind double-stranded DNA (dsDNA) and their L chain sequences showed a biased use of V(kappa) and J(kappa) gene segments. The 44 L chains in this survey were coded for by just 18 germline genes. Six of the genes, each belonging to a different V(kappa) group, were used more than once and accounted for three fourths of all sequences. Based on the distribution of V(kappa) genes, the L chain repertoire in this line of transgenic mice was estimated at 37 V(kappa) genes. The most frequently observed gene, a member of the V(kappa) 12/13 group, was identified in 16 hybrids. In addition, the majority of V(kappa) genes used J(kappa)5. We interpret the skewed representation of V(kappa) and J(kappa) gene segments to result from negative selection. Based on the data, we suggest that V(kappa) rearrangements giving rise to anti-dsDNA reactivity are removed from the repertoire by a corrective mechanism capable of editing self-reactive Ig.