IgA and IgM V(H) repertoires in human colon: evidence for clonally expanded B cells that are widely disseminated.
OBJECTIVE
The mucosal immune system defends the body from pathogens to which the mucosal surfaces are continually exposed. Because lamina propria B cells should reflect the antigenic experience of the gut, we investigated their immunoglobulin (Ig) repertoire and distribution.


METHODS
The junctional diversity of the IgA and IgM heavy-chain transcripts in the colon and the peripheral blood of healthy adults was analyzed by CDR3 size spectratyping and nucleotide sequencing.


RESULTS
The V(H)6 and V(H)7 repertoires of intestinal IgA and IgM cells were oligoclonal, whereas the CDR3 profiles of the larger V(H)1-V(H)5 families suggested a more diverse repertoire with dominant bands superimposed on a polyclonal background. However, sequence analysis revealed multiple repetitive and clonally related transcripts at distant colonic sites from all V(H) families. This suggests that, in addition to a polyclonal B-cell pool, subsets of B cells are clonally expanded and 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) repertoire that was distinct from that in the colon.


CONCLUSIONS
The human colon contains widely disseminated B cells that express clonally related IgA or IgM receptors. These results are best explained by an antigen-driven process whereby intestinal memory B cells continuously recirculate.
Holtmeier
W
W
Medizinische Klinik II, Johann-Wolfgang Goethe Universitdt, Frankfurt am Main, Germany. W.Holtmeier@em.uni-frankfurt.de
Hennemann
A
A
Caspary
W F
WF
D000595:Amino Acid Sequence / Q000235:genetics; D016175:B-Lymphocyte Subsets / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology / Q000378:metabolism; D001483:Base Sequence / Q000235:genetics; D001773:Blood Cells / Q000378:metabolism; D002999:Clone Cells; D003106:Colon / Q000166:cytology / Q000378:metabolism*; D022801:Complementarity Determining Regions; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics / Q000378:metabolism*; D007143:Immunoglobulin Heavy Chains / Q000378:metabolism; D007132:Immunoglobulin Isotypes / Q000378:metabolism; D007075:Immunoglobulin M / Q000235:genetics / Q000378:metabolism*; D007134:Immunoglobulin Switch Region / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism*; D018655:Lymphocyte Count; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics / Q000502:physiology
D022801:Complementarity Determining Regions; D007070:Immunoglobulin A; D007143:Immunoglobulin Heavy Chains; D007132:Immunoglobulin Isotypes; D007075:Immunoglobulin M; D007135:Immunoglobulin Variable Region