| First Author | Wesemann DR | Year | 2013 |
| Journal | Nature | Volume | 501 |
| Issue | 7465 | Pages | 112-5 |
| PubMed ID | 23965619 | Mgi Jnum | J:205432 |
| Mgi Id | MGI:5544863 | Doi | 10.1038/nature12496 |
| Citation | Wesemann DR, et al. (2013) Microbial colonization influences early B-lineage development in the gut lamina propria. Nature 501(7465):112-5 |
| abstractText | The RAG1/RAG2 endonuclease (RAG) initiates the V(D)J recombination reaction that assembles immunoglobulin heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires. IgH V(D)J assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor (pre-) B cells. Expression of IgH mu and IgL (Igkappa or Iglambda) chains generates IgM, which is expressed on immature B cells as the B-cell antigen-binding receptor (BCR). Rag expression can continue in immature B cells, allowing continued Igkappa V(D)J recombination that replaces the initial VkappaJkappa exon with one that generates a new specificity. This 'receptor editing' process, which can also lead to Iglambda V(D)J recombination and expression, provides a mechanism whereby antigen encounter at the Rag-expressing immature B-cell stage helps shape pre-immune BCR repertoires. As the major site of postnatal B-cell development, the bone marrow is the principal location of primary immunoglobulin repertoire diversification in mice. Here we report that early B-cell development also occurs within the mouse intestinal lamina propria (LP), where the associated V(D)J recombination/receptor editing processes modulate primary LP immunoglobulin repertoires. At weanling age in normally housed mice, the LP contains a population of Rag-expressing B-lineage cells that harbour intermediates indicative of ongoing V(D)J recombination and which contain cells with pro-B, pre-B and editing phenotypes. Consistent with LP-specific receptor editing, Rag-expressing LP B-lineage cells have similar VH repertoires, but significantly different Vkappa repertoires, compared to those of Rag2-expressing bone marrow counterparts. Moreover, colonization of germ-free mice leads to an increased ratio of Iglambda-expressing versus Igkappa-expressing B cells specifically in the LP. We conclude that B-cell development occurs in the intestinal mucosa, where it is regulated by extracellular signals from commensal microbes that influence gut immunoglobulin repertoires. |
