Cargando…
Microbial colonization influences early B-lineage development in the gut lamina propria
The RAG1/RAG2 endonuclease ("RAG") initiates the V(D)J recombination reaction that assembles Ig heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires(1). IgH V(D)J assembly occurs in progenitor (pro-) B cells followed b...
Autores principales: | , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
2013
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807868/ https://www.ncbi.nlm.nih.gov/pubmed/23965619 http://dx.doi.org/10.1038/nature12496 |
_version_ | 1782288520060076032 |
---|---|
author | Wesemann, Duane R. Portuguese, Andrew J. Meyers, Robin M. Gallagher, Michael P. Cluff-Jones, Kendra Magee, Jennifer M. Panchakshari, Rohit A. Rodig, Scott J. Kepler, Thomas B. Alt, Frederick W. |
author_facet | Wesemann, Duane R. Portuguese, Andrew J. Meyers, Robin M. Gallagher, Michael P. Cluff-Jones, Kendra Magee, Jennifer M. Panchakshari, Rohit A. Rodig, Scott J. Kepler, Thomas B. Alt, Frederick W. |
author_sort | Wesemann, Duane R. |
collection | PubMed |
description | The RAG1/RAG2 endonuclease ("RAG") initiates the V(D)J recombination reaction that assembles Ig heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires(1). IgH V(D)J assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor (pre-) B cells. Expression of IgH μ and IgL (Igκ or Igλ) 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(2), allowing continued Igκ V(D)J recombination that replaces the initial VκJκ exon with one that generates a new specificity(3–5). This “receptor editing” process, which also can lead to Igλ V(D)J recombination and expression(3,6,7), 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 post-natal B cell development, the bone marrow is the principal location of primary Ig 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 Ig repertoires. At weanling age in normally housed mice, the LP contains a population of Rag-expressing B lineage cells that harbor 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 V(H) repertoires, but significantly different Vκ repertoires, compared to those of Rag2-expressing BM counterparts. Moreover, colonization of germ-free mice leads to an increased ratio of Igλ-expressing versus Igκ-expressing B cells specifically in the LP. We conclude that B cell development occurs in the intestinal mucosa, where it is regulated by extra-cellular signals from commensal microbes that influence gut Ig repertoires. |
format | Online Article Text |
id | pubmed-3807868 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2013 |
record_format | MEDLINE/PubMed |
spelling | pubmed-38078682014-03-05 Microbial colonization influences early B-lineage development in the gut lamina propria Wesemann, Duane R. Portuguese, Andrew J. Meyers, Robin M. Gallagher, Michael P. Cluff-Jones, Kendra Magee, Jennifer M. Panchakshari, Rohit A. Rodig, Scott J. Kepler, Thomas B. Alt, Frederick W. Nature Article The RAG1/RAG2 endonuclease ("RAG") initiates the V(D)J recombination reaction that assembles Ig heavy (IgH) and light (IgL) chain variable region exons from germline gene segments to generate primary antibody repertoires(1). IgH V(D)J assembly occurs in progenitor (pro-) B cells followed by that of IgL in precursor (pre-) B cells. Expression of IgH μ and IgL (Igκ or Igλ) 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(2), allowing continued Igκ V(D)J recombination that replaces the initial VκJκ exon with one that generates a new specificity(3–5). This “receptor editing” process, which also can lead to Igλ V(D)J recombination and expression(3,6,7), 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 post-natal B cell development, the bone marrow is the principal location of primary Ig 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 Ig repertoires. At weanling age in normally housed mice, the LP contains a population of Rag-expressing B lineage cells that harbor 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 V(H) repertoires, but significantly different Vκ repertoires, compared to those of Rag2-expressing BM counterparts. Moreover, colonization of germ-free mice leads to an increased ratio of Igλ-expressing versus Igκ-expressing B cells specifically in the LP. We conclude that B cell development occurs in the intestinal mucosa, where it is regulated by extra-cellular signals from commensal microbes that influence gut Ig repertoires. 2013-08-21 2013-09-05 /pmc/articles/PMC3807868/ /pubmed/23965619 http://dx.doi.org/10.1038/nature12496 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms |
spellingShingle | Article Wesemann, Duane R. Portuguese, Andrew J. Meyers, Robin M. Gallagher, Michael P. Cluff-Jones, Kendra Magee, Jennifer M. Panchakshari, Rohit A. Rodig, Scott J. Kepler, Thomas B. Alt, Frederick W. Microbial colonization influences early B-lineage development in the gut lamina propria |
title | Microbial colonization influences early B-lineage development in the gut lamina propria |
title_full | Microbial colonization influences early B-lineage development in the gut lamina propria |
title_fullStr | Microbial colonization influences early B-lineage development in the gut lamina propria |
title_full_unstemmed | Microbial colonization influences early B-lineage development in the gut lamina propria |
title_short | Microbial colonization influences early B-lineage development in the gut lamina propria |
title_sort | microbial colonization influences early b-lineage development in the gut lamina propria |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3807868/ https://www.ncbi.nlm.nih.gov/pubmed/23965619 http://dx.doi.org/10.1038/nature12496 |
work_keys_str_mv | AT wesemannduaner microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT portugueseandrewj microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT meyersrobinm microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT gallaghermichaelp microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT cluffjoneskendra microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT mageejenniferm microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT panchaksharirohita microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT rodigscottj microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT keplerthomasb microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria AT altfrederickw microbialcolonizationinfluencesearlyblineagedevelopmentinthegutlaminapropria |