SOMATIC HYPERMUTATION OF V(H)S107 GENES IS NOT ASSOCIATED WITH GENE CONVERSION AMONG FAMILY MEMBERS

Murine a cells proliferating in the germinal centers of peripheral lymphoid tissue accumulate mutations in their rearranged variable regions, a diversification process which contributes to affinity maturation of the antibody response. The highly targeted nature of the hypermutation process could be explained by a somatic gene conversion mechanism. Well characterized examples of such an activity in a cells are seen during diversification of the chicken and rabbit Ig repertoires. The genomic organization, low complexity and high degree of homology exhibited by the four members of the murine V(H)S107 gene family suggested that these gene segments may be suitable candidates for the search of gene conversion events derived from upstream V(H)S107 counterparts. After an immune response to a complex T cell-dependent antigen (sheep red blood cells), rearranged V13, V11 and V1 genes were isolated from splenic extrafollicular and germinal center a cells. Extensive somatic mutation was evident in V11 and V1 sequences. When these sequences were examined, as well as V1 sequences isolated from phosphorylcholine-specific hybridomas, the observed nucleotide changes were not associated with any gene conversion between family members, suggesting instead that they arose by a mechanism which introduces point mutations.