B lymphocytes may escape tolerance by revising their antigen receptors.

MZ Radic, J Erikson, S Litwin, M Weigert - The Journal of experimental …, 1993 - rupress.org
MZ Radic, J Erikson, S Litwin, M Weigert
The Journal of experimental medicine, 1993rupress.org
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 …
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.
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