Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin (antibody sequences/antibody genes/somatic mutation)

摘要

ABSTRACT We have examined the ammo-terminal sequence of the k light chains of a set of monoclonal antibodies specific for one of the major antigenic determinants (Sb) on the influenza virus PR8[A/PR/8/34(HlNl)] hemagglutinin molecule. This set was believed to be structurally related from earlier serological analysis that typed these k chains as members of the variable (V) region V_K21 group [Staudl, L. M. & Gerhard, W. (1983) J. Exp. Med. 157, 678-704]. Our sequence analysis confirms and extends this conclusion; all examples of this set belong to a subgroup of the V_k group, V_K21C. A special feature of this set of k light chains is that all examples were derived from the same mouse (designated H36). This sequence analysis along with the characterization of gene rearrangements at the k light chain loci of these hybridomas is consistent with the idea that certain members of this set are the progeny of one or two lymphocytes. Because of this potential clonal relationship, we can reach several conclusionsabout the diversity observed among these k light chains: (0 the diversity is due to somatic mutation, (it) somatic mutations occur sequentially and accumulate in the first complementarity-determining region, and (iii) the extent of somatic variation in this sample is high, suggesting a somatic mutation rate of about 10~(10) per base pair per generation.