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Gastroenterology. 2000 Nov;119(5):1253-66.

IgA and IgM V(H) repertoires in human colon: evidence for clonally expanded B cells that are widely disseminated.

Author information

1
Medizinische Klinik II, Johann-Wolfgang Goethe Universitdt, Frankfurt am Main, Germany. W.Holtmeier@em.uni-frankfurt.de

Abstract

BACKGROUND & AIMS:

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.

PMID:
11054383
DOI:
10.1053/gast.2000.20219
[Indexed for MEDLINE]

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