Characteristics of IgV(H) genes used by human intestinal plasma cells fromchildhood

Plasma cells secreting immunoglobulin M (IgM) and IgA in human:intestinal m ucosa are the largest antibody-producing population in the human body. Desp ite this there have been relatively few studies of the characteristics and maturation of the genes which encode the mucosal immunoglobulins. We have p reviously demonstrated that intestinal plasma cells use highly mutated IgV( H) genes, likely to reflect germinal centre origin. Here we show that IgV(H ) genes used by intestinal lamina propria plasma cells secreting IgM and Ig A are highly mutated from childhood, with no change in the frequency of mut ation through to adulthood, though IgV(H) genes used. by IgM are significan tly less mutated than those used by IgA. There was no difference between th e IgA subclasses in either the frequency or distribution of mutations. The Frequency of mutation in IgV(H)4-34 genes used by IgG was also studied in t he adult biopsies, and was found to be of the same order as that observed i n IgA and was significantly higher than that observed in IgM. We have ident ified IgM and IgA sequences which share identical CDR3 and distribution of mutations. Isotype switching may therefore occur after extensive mutation o f IgM sequences; and IgM- and IgA-secreting plasma cells with the same spec ificity may occur within the same microenvironment. IgM should therefore be considered to be a component of secondary immune responses in the gut.