Cutting Edge: Retinoic Acid Signaling in B Cells Is Essential for Oral Immunization and Microflora Composition

J Immunol. 2015 Aug 15;195(4):1368-71. doi: 10.4049/jimmunol.1500989. Epub 2015 Jul 10.

Abstract

Retinoic acid (RA) is a critical regulator of the intestinal adaptive immune response. However, the intrinsic impact of RA on B cell differentiation in the regulation of gut humoral immunity in vivo has never been directly shown. To address this issue, we have been able to generate a mouse model where B cells specifically express a dominant-negative receptor α for RA. In this study, we show that the silencing of RA signaling in B cells reduces the numbers of IgA(+) Ab-secreting cells both in vitro and in vivo, suggesting that RA has a direct effect on IgA plasma cell differentiation. Moreover, the lack of RA signaling in B cells abrogates Ag-specific IgA responses after oral immunization and affects the microbiota composition. In conclusion, these results suggest that RA signaling in B cells through the RA receptor α is important to generate an effective gut humoral response and to maintain a normal microbiota composition.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism*
  • Cell Differentiation / immunology
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / microbiology
  • Gene Expression
  • Immunization*
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin A / immunology
  • Mice
  • Mice, Transgenic
  • Microbiota / immunology
  • Plasma Cells / cytology
  • Plasma Cells / immunology
  • Plasma Cells / metabolism
  • Receptors, Retinoic Acid / genetics
  • Receptors, Retinoic Acid / metabolism
  • Signal Transduction*
  • Tretinoin / metabolism*

Substances

  • Immunoglobulin A
  • Receptors, Retinoic Acid
  • Tretinoin