V region gene usage and somatic mutation in the primary and secondary responses to influenza virus hemagglutinin

Most (80 to 90%) primary antibodies specific for the Sb site of influenza virus (A/PR/8/34) hemagglutinin share an Id (designated C4). Secondary antihemagglutinin(Sb) antibodies also exhibit the C4 Id although less frequently (10 to 15%). We have analyzed the V region nucleotide sequences of primary and secondary antibodies with the C4 Id. Primary C4 antibodies are encoded by the same Vk gene, belonging to the Vk8 group, usually rearranged to Jk5. The H chains are diverse, encoded by VH genes belonging to at least four different VH families, a variety of DH genes, and either JH2, JH3, or JH4. There is only one somatic mutation among seven Vk and two VH genes encoding primary C4 antibodies. Secondary C4 antibodies are also encoded by the same Vk8-Jk5 gene segment and by diverse VH genes. Additional heterogeneity in the secondary response is caused by somatic mutation.