INTERCLONAL AND INTRACLONAL DIVERSITY IN THE ANTIBODY-RESPONSE TO INFLUENZA HEMAGGLUTININ

This study focuses on 10 BALB/c antiinfluenza virus (A/PR/8/34) hemagglutinin antibodies that have L chains encoded by the same variable region .kappa. chains (V.kappa.) gene, V.kappa.21C. A comparison of antibodies from lymphocytes of independent origin reveals the contribution of germline diversity (combinatorial joining and association) to this response. Although combinatorial joining and association contribute to sequence diversity, they appear to have little effect on the fine specificity of these antibodies. Somatic mutation, in addition to contributing to the sequence diversity of these antibodies, creates differences in their fine specificity. The extent of mutation and its effect on fine specificity can be seen by comparing antibodies of lymphocytes from the same clone. These intraclonal comparisons also indicate that somatic mutation is an ongoing process occurring at a high rate (estimated to be at least 10-3 mutations/base pair/division) in the expressed V region H chain (VH) and V.kappa. genes. Both the nature and distribution of these mutations suggest that amino acid replacement mutations in the L but not the H chain are selected for by antigen.