Tolerogenic CX3CR1+ B cells suppress food allergy-induced intestinal inflammation in mice

Allergy. 2013 Oct;68(10):1241-8. doi: 10.1111/all.12218. Epub 2013 Sep 4.

Abstract

Background: B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet.

Objective: This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy-induced intestinal inflammation in mice.

Methods: The intestinal mucosa-derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs.

Results: A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)-β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti-IgM antibody induced naive B cells to differentiate into the TGF-β-producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced intestinal Th2 pattern inflammation in mice.

Conclusions: CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy-related Th2 pattern inflammation in mice.

Keywords: Th2 response; food allergy; intestine; regulatory T cell; tolerogenic B cell.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigens, Neoplasm / metabolism
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • CX3C Chemokine Receptor 1
  • Disease Models, Animal
  • Enteritis / etiology*
  • Enteritis / metabolism*
  • Food Hypersensitivity / complications*
  • Food Hypersensitivity / metabolism*
  • Food Hypersensitivity / therapy
  • Immune Tolerance*
  • Integrins / metabolism
  • Intestinal Mucosa / immunology
  • Intestinal Mucosa / metabolism
  • Intestinal Mucosa / pathology
  • Lymphocyte Activation / immunology
  • Mice
  • Receptors, Chemokine / metabolism*
  • T-Lymphocyte Subsets / immunology
  • T-Lymphocyte Subsets / metabolism
  • T-Lymphocytes, Regulatory / immunology
  • T-Lymphocytes, Regulatory / metabolism
  • Th2 Cells / immunology
  • Th2 Cells / metabolism
  • Transforming Growth Factor beta / metabolism

Substances

  • Antigens, Neoplasm
  • CX3C Chemokine Receptor 1
  • Cx3cr1 protein, mouse
  • Integrins
  • Receptors, Chemokine
  • Transforming Growth Factor beta
  • integrin alphavbeta6