Published online before print January 23, 2009
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,1
* Department of Molecular Bioscience, School of Bioscience and Biotechnology, and
Vascular System Research Center, Kangwon National University, Chuncheon, Korea; and
Department of Anatomy and Cell Biology, Institute of Biomedical Science, Hanyang University, Seoul, Korea
1 Correspondence: Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea. E-mail: phkim{at}kangwon.ac.kr
ABSTRACT
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
(GL
)/GL
2b 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
and GL
2b promoters. These results indicate that IL-21 decreases IgG2b secretion mainly through inhibition of GL
2b 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 Peyers patches (PP) than in spleen. These results suggest that IL-21 has an important effect on selective IgA+ B cell commitment in PP.
Key Words: class switch promoter germ line transcript