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Published online before print March 19, 2008
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© by The Society for Leukocyte Biology
Journal of Leukocyte Biology, doi:10.1189/jlb.1007710

Received for publication October 26, 2007.
Revised February 5, 2008.
Accepted for publication February 18, 2008.

Article

A dual role of activin A in regulating immunoglobulin production of B cells

Kenji Ogawa *@, Masayuki Funaba {dagger}, and Masafumi Tsujimoto *

*Laboratory of Cellular Biochemistry, RIKEN, Wako, Saitama, Japan; and {dagger}Laboratory of Nutrition, Azabu University School of Veterinary Medicine, Sagamihara, Kanagawa, Japan

@ To whom correspondence should be addressed. E-mail: kkogawa{at}riken.jp.


  Abstract

Here, we report that activin A has a dual role in regulating Ig production of murine B cells. Activated B cells secrete activin activity by increasing activin A and decreasing follistatin expression. B cells also express type I and type II activin receptors, suggesting that they are targets of activin. Pretreatment of naïve B cells with activin A and subsequent activation by LPS resulted in increased cell growth and IgG production. In contrast, no significant effect was observed when activin A was added to naïve B cells simultaneously with LPS, indicating that activin A acts on resting but not activated B cells. In addition, activin A did not induce B cells to produce IgE, even when added prior to activation; however, in vivo antigen-specific IgE production was reduced significantly by neutralization of circulating activin A. These findings indicate that activin A plays an important role in Th2-mediated immune responses by enhancing antibody production through two distinct modes: acts directly on resting B cells to elicit full functions of activated B cells and acts indirectly on activated B cells through modulation of other immune cells.

Key Words: class-switch recombination • mouse • TGF-{beta}






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