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

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

Author information

1
Department of Immune Regulation and Intervention, Division of Transplantation Immunology and Mucosal Biology, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom;
2
Department of Mucosal Immunology, Division of Transplantation Immunology and Mucosal Biology, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom;
3
Division of Diabetes and Nutritional Sciences, King's College London, London SE1 1UL, United Kingdom;
4
Mucosal Immunobiology and Vaccines Center, Department of Microbiology and Immunology, Institute of Biomedicine, University of Gothenburg, 405 30 Gothenburg, Sweden; and.
5
Department of Immune Regulation and Intervention, Division of Transplantation Immunology and Mucosal Biology, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom; Department of Microbiology and Immunology, Dartmouth Medical School and Norris Cotton Cancer Center, Lebanon, NH 03755 Randolph.J.Noelle@Dartmouth.edu raul.elgueta@kcl.ac.uk.
6
Department of Immune Regulation and Intervention, Division of Transplantation Immunology and Mucosal Biology, Guy's Hospital, King's College London, London SE1 9RT, United Kingdom; Randolph.J.Noelle@Dartmouth.edu raul.elgueta@kcl.ac.uk.

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.

PMID:
26163586
PMCID:
PMC4539572
DOI:
10.4049/jimmunol.1500989
[Indexed for MEDLINE]
Free PMC Article

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