Proc Natl Acad Sci U S A. 2005 Feb 8;102(6):2010-5. Epub 2005 Jan 31.

Mesenteric B cells centrally inhibit CD4+ T cell colitis through interaction with regulatory T cell subsets.

Wei B, Velazquez P, Turovskaya O, Spricher K, Aranda R, Kronenberg M, Birnbaumer L, Braun J.

Source

Department of Pathology and Laboratory Medicine and Molecular Biology Institute, University of California, Los Angeles, CA 90095, USA.

Abstract

Inflammatory bowel disease reflects an aberrant mucosal CD4+ T cell response to commensal enteric bacteria. In addition to regulatory T cell subsets, recent studies have revealed a protective role of B cells in murine CD4+ T cell colitis, but the relationship of their action to T cell immunoregulation is unknown. Here we report that mesenteric lymph node (MLN) B cells protect mice from colitis induced by Galphai2-/- CD4+ T cells. Protection required the transfer of both B cells and CD8alpha+ T cells; neither cell type alone was sufficient to inhibit CD4+ T cell-mediated colitis. Similar results were also observed in colitis induced by CD4+CD45RBhi T cells. Immunoregulation was associated with localization of B cells and expansion of CD4-CD8- CD3+NK1.1+ T cells in the secondary lymphoid compartment, as well as expansion of CD4+CD8alpha+ T cells in the intestinal intraepithelial compartment. MLN B cells from Galphai2-/- mice were deficient in a phenotypic subset and failed to provide cotransfer colitis protection. These findings indicate that protective action of B cells is a selective trait of MLN B cells acquired through a Galphai2-dependent developmental process and link B cells with the formation of regulatory T cells associated with mucosal immune homeostasis.