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

• Published in: Journal of leukocyte biology Vol. 94; no. 2; pp. 325 - 335
• Main Authors: Seo, Goo‐Young, Jang, Young‐Saeng, Kim, Hyun‐A, Lee, Mi‐Ra, Park, Mi‐Hee, Park, Seok‐Rae, Lee, Jeong‐Min, Choe, Jongseon, Kim, Pyeung‐Hyeun
• Format: Journal Article
• Language: English
• Published: United States Society for Leukocyte Biology 01.08.2013
• Subjects: Animals; Cells, Cultured - immunology; class switch; Clonal Selection, Antigen-Mediated; Endotoxins - toxicity; Genes, Immunoglobulin; gut‐homing molecule; 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; mucosal immunity; 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; gut-homing molecule; class switch; mucosal immunity
• ISSN: 0741-5400; 1938-3673
• DOI: 10.1189/jlb.0313128

Retinoic acid, in cooperation with TGF‐β1, increases IgA class switching and expression of gut‐homing molecules CCR9 and α4β7, on mouse B cells. 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.