Premium
IL‐21 ensures TGF‐β1‐induced IgA isotype expression in mouse Peyer's patches
Author(s) -
Seo GooYoung,
Youn Jeehee,
Kim PyeungHyeun
Publication year - 2009
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.0708450
Subject(s) - isotype , biology , secretion , immunoglobulin class switching , transforming growth factor , peyer's patch , microbiology and biotechnology , antibody , interleukin 4 , spleen , interleukin 10 , immunology , immune system , endocrinology , b cell , monoclonal antibody
It is well established that TGF‐β1 induces IgA and IgG2b class‐switching recombination in murine B cells. In the present study, we assessed the activity of IL‐21 along with TGF‐β1 in Ig synthesis by murine spleen B cells. IL‐21 showed antiproliferative activity on LPS‐activated splenic B cells, comparable with that of TGF‐β1. IL‐21 alone had little effect on IgA secretion and decreased other isotypes. Likewise, IL‐21 also did not alter the TGF‐β1‐induced IgA synthesis and concurrently diminished the syntheses of IgM and IgG2a, which were repressed by TGF‐β1. Unexpectedly, IL‐21 inhibited the TGF‐β1‐induced IgG2b production. This IL‐21 effect was examined using B cells from IL‐21R knockout mice, where the IgA production profile was paralleled by that seen in wild‐type B cells. However, the inhibitory effect of IL‐21 on TGF‐β1‐induced IgG2b synthesis was not seen in the IL‐21R −/− mouse, suggesting that IL‐21 causes TGF‐β1‐stimulated B cells to decrease IgG2b synthesis. Expression patterns of Ig germ‐line α(GLα)/GLγ2b transcripts under the influence of TGF‐β1 and IL‐21 were paralleled by IgA/IgG2b secretion. This was also observed in the activities of GL α and GL γ2b promoters. These results indicate that IL‐21 decreases IgG2b secretion mainly through inhibition of GL γ2b transcription and is ultimately associated with selective IgA secretion induced by TGF‐β1. Our results showed that IL‐21 was expressed in greater magnitude in Peyer's patches (PP) than in spleen. These results suggest that IL‐21 has an important effect on selective IgA + B cell commitment in PP.