IL-21 ensures TGF-beta 1-induced IgA isotype expression in mouse Peyer's patches.
It is well established that TGF-beta1 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-beta1 in Ig synthesis by murine spleen B cells. IL-21 showed antiproliferative activity on LPS-activated splenic B cells, comparable with that of TGF-beta1. IL-21 alone had little effect on IgA secretion and decreased other isotypes. Likewise, IL-21 also did not alter the TGF-beta1-induced IgA synthesis and concurrently diminished the syntheses of IgM and IgG2a, which were repressed by TGF-beta1. Unexpectedly, IL-21 inhibited the TGF-beta1-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-beta1-induced IgG2b synthesis was not seen in the IL-21R(-/-) mouse, suggesting that IL-21 causes TGF-beta1-stimulated B cells to decrease IgG2b synthesis. Expression patterns of Ig germ-line alpha(GL alpha)/GL gamma 2b transcripts under the influence of TGF-beta1 and IL-21 were paralleled by IgA/IgG2b secretion. This was also observed in the activities of GL(alpha) and GL(gamma 2b) promoters. These results indicate that IL-21 decreases IgG2b secretion mainly through inhibition of GL(gamma 2b) transcription and is ultimately associated with selective IgA secretion induced by TGF-beta1. 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.
Seo
Goo-Young
GY
Department of Molecular Bioscience, School of Bioscience and Biotechnology, Kangwon National University, Chuncheon 200-701, Korea.
Youn
Jeehee
J
Kim
Pyeung-Hyeun
PH
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology / Q000378:metabolism; D049109:Cell Proliferation; D002478:Cells, Cultured; D005786:Gene Expression Regulation; D007070:Immunoglobulin A / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching; D007074:Immunoglobulin G / Q000096:biosynthesis; D007132:Immunoglobulin Isotypes / Q000276:immunology / Q000378:metabolism*; D007378:Interleukins / Q000276:immunology / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010581:Peyer's Patches / Q000276:immunology / Q000378:metabolism*; D013154:Spleen / Q000166:cytology / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*; D000098546:Interleukin-21
D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007132:Immunoglobulin Isotypes; D007378:Interleukins; D053773:Transforming Growth Factor beta1; D000098546:Interleukin-21