Retinoic acid, acting as a highly specific IgA isotype switch factor, cooperates with TGF-β1 to enhance the overall IgA response

J Leukoc Biol. 2013 Aug;94(2):325-35. doi: 10.1189/jlb.0313128. Epub 2013 Jun 6.


The present study demonstrates that RA has activity of an IgA switch factor and is more specific than TGF-β1. RA independently caused only IgA switching, whereas TGF-β1 caused IgA and IgG2b switching. We found that RA increased IgA production and that this was a result of its ability to increase the frequency of IgA-secreting B cell clones. Increased IgA production was accompanied by an increase of GLTα. RA activity was abrogated by an antagonist of the RAR. Additionally, RA affected intestinal IgA production in mice. Surprisingly, RA, in combination with TGF-β1, notably enhanced not only IgA production and GLTα expression but also CCR9 and α4β7 expression on B cells. These results suggest that RA selectively induces IgA isotype switching through RAR and that RA and TGF-β have important effects on the overall gut IgA antibody response.

Keywords: class switch; gut-homing molecule; mucosal immunity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cells, Cultured / immunology
  • Clonal Selection, Antigen-Mediated
  • Endotoxins / toxicity
  • Genes, Immunoglobulin
  • Immunity, Mucosal / drug effects
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin A / immunology*
  • Immunoglobulin Class Switching / drug effects*
  • Immunoglobulin G / immunology
  • Integrins / biosynthesis
  • Integrins / genetics
  • Lymph Nodes / immunology
  • Mesentery / immunology
  • Mice
  • Mice, Inbred BALB C
  • Peyer's Patches / immunology
  • Receptors, CCR / biosynthesis
  • Receptors, CCR / genetics
  • Receptors, Lymphocyte Homing / drug effects
  • Receptors, Lymphocyte Homing / immunology
  • Receptors, Retinoic Acid / physiology
  • Transforming Growth Factor beta1 / immunology*
  • Tretinoin / pharmacology*


  • CC chemokine receptor 9
  • Endotoxins
  • Immunoglobulin A
  • Immunoglobulin G
  • Integrins
  • Receptors, CCR
  • Receptors, Lymphocyte Homing
  • Receptors, Retinoic Acid
  • Transforming Growth Factor beta1
  • integrin alpha4beta7
  • Tretinoin
  • endotoxin, Escherichia coli