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

Gastroenterology. 2000 Nov;119(5):1253-66. doi: 10.1053/gast.2000.20219.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence / genetics
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocytes / cytology
  • B-Lymphocytes / metabolism
  • Base Sequence / genetics
  • Blood Cells / metabolism
  • Clone Cells
  • Colon / cytology
  • Colon / metabolism*
  • Complementarity Determining Regions
  • Humans
  • Immunoglobulin A / genetics
  • Immunoglobulin A / metabolism*
  • Immunoglobulin Heavy Chains / metabolism
  • Immunoglobulin Isotypes / metabolism
  • Immunoglobulin M / genetics
  • Immunoglobulin M / metabolism*
  • Immunoglobulin Switch Region / genetics
  • Immunoglobulin Variable Region / genetics
  • Immunoglobulin Variable Region / metabolism*
  • Lymphocyte Count
  • Molecular Sequence Data
  • Mutation / genetics
  • Mutation / physiology


  • Complementarity Determining Regions
  • Immunoglobulin A
  • Immunoglobulin Heavy Chains
  • Immunoglobulin Isotypes
  • Immunoglobulin M
  • Immunoglobulin Variable Region

Associated data

  • GENBANK/AF267756
  • GENBANK/AF267808
  • GENBANK/AF267809
  • GENBANK/AF267847