IgA and IgM V-H repertoires in human colon: Evidence for clonally expandedB cells that are widely disseminated

Background & Aims: The mucosal immune system defends the body from pathogen s to which the mucosal surfaces are continually exposed. Because lamina pro pria B cells should reflect the antigenic experience of the gut, we investi gated their immunoglobulin (Ig) repertoire and distribution. Methods: The j unctional diversity of the IgA and IgM heavy-chain transcripts in the colon and the peripheral blood of healthy adults was analyzed by CDR3 size spect ratyping and nucleotide sequencing. Results: The V(H)6 and V(H)7 repertoire s of intestinal IgA and IgM cells were oligoclonal, whereas the CDR3 profil es of the larger V(H)1-V(H)5 families suggested a more diverse repertoire w ith dominant bands superimposed on a polyclonal background. However, sequen ce analysis revealed multiple repetitive and clonally related transcripts a t distant colonic sites from all V-H families. This suggests that, in addit ion to a polyclonal B-cell pool, subsets of B cells are clonally expanded a nd widely distributed along the colon. Occasionally, there was evidence for B cells with the same CDR3 specificity, which exhibited an isotype switch from IgM to IgA. Circulating IgA B cells expressed a restricted V-H reperto ire that was distinct from that in the colon. Conclusions: The human colon contains widely disseminated B cells that express clonally related IgA or I gM receptors. These results are best explained by an antigen-driven process whereby intestinal memory B cells continuously recirculate.