Human IgA- and IgM-secreting intestinal plasma cells carry heavily mutated VH region genes

Single IgA- or IgM-secreting plasma cells were isolated from histological sections of human jejunum and terminal ileum, and Ig heavy chain variable (VH) region genes were amplified and sequenced. Taken together, 62 of 63 cells analyzed harbored somatically mutated VH region genes, indicating that the vast majority of both IgA- and IgM-secreting intestinal plasma cells derive from germinal center B cells. On average, rearranged VH genes of IgA- and IgM-secreting plasma cells showed a mutation frequency of 9.0 % and 8.5 %, respectively, which exceeds the level of somatic mutation of V region genes carried by human memory B cells. Moreover, we detected deletions or insertions in the complementarity-determining regions of 5 of the 58 functional VH region genes analyzed, suggesting that these alterations may contribute to the diversification of the human antibody repertoire in the course of an immune reaction.