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.
Radic
M Z
MZ
Institute for Cancer Research, Fox Chase Cancer Center, Philadelphia, Pennsylvania 19111.
Erikson
J
J
Litwin
S
S
Weigert
M
M
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D015139:Blotting, Southern; D004247:DNA; D005260:Female; D015322:Gene Rearrangement, B-Lymphocyte; D006825:Hybridomas; D007108:Immune Tolerance; D007133:Immunoglobulin Joining Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D051379:Mice; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000276:immunology*
D007133:Immunoglobulin Joining Region; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell; D004247:DNA