Generation of antibody diversity in the immune response of BALB/c mice to influenza virus hemagglutinin.

Abstract

The amino-terminal sequence of the .kappa. L-chains of a set of mouse monoclonal antibodies specific for 1 of the major antigenic determinants (Sb) on the influenza virus PR8[A/PR/8/34(H1N1)]hemagglutinin molecule was studied. This set was believed to be structurally related from earlier serological analysis that typed these .kappa. chains as members of the variable (V) region V.kappa.21 group. Sequence analysis confirms and extends this conclusion; all examples of this set belong to a subgroup of the V.kappa.21 group, V.kappa.21C. A special feature of this set of .kappa. L 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 .kappa. L chain loci of these hybridomas is consistent with the idea that certain members of this set are the progeny of 1 or 2 lymphocytes. Because of this potential clonal relationship, several conclusions can be reached about the diversity observed among these .kappa. L chains; the diversity is due to somatic mutation, somatic mutations occur sequentially and accumulate in the first complementarity-determining region and the extent of somatic variation in this sample is high, suggesting a somatic mutation rate of .apprx. 10-3/base pair/generation.