The Journal of Experimental Medicine
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Published online 11 August 2003 doi:10.1084/jem.20030280
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© Rockefeller University Press, 0022-1007/2003/8/581 $5.00
The Journal of Experimental Medicine, Volume 198, Number 4, 581-589

Coupling Between B Cell Receptor and Phospholipase C-{gamma}2 Is Essential for Mature B Cell Development

Masaki Hikida1, Sachiko Johmura1, Ari Hashimoto1, Mayuko Takezaki2 and Tomohiro Kurosaki1,2

1 Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University
2 Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, 10-15 Fumizono-cho, Moriguchi 570-8506, Japan

Address correspondence to Tomohiro Kurosaki, Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan. Phone: 81-6-6993-9445; Fax: 81-6-6994-6099; email: kurosaki{at}mxr.mesh.ne.jp

Two signaling pathways known to be essential for progression from immature to mature B cells are BAFF receptor (BAFF-R) and the B cell receptor (BCR). Here, we first show that phospholipase C (PLC)-{gamma}2 is required for a BAFF-R–mediated survival signal. Then, we have examined the question of whether the reduced number of mature B cells in PLC-{gamma}2-/- mice is caused by a defect in either BCR or BAFF-R signaling. We find that a PLC-{gamma}2 SH2 mutant, which inhibits coupling between BCR and PLC-{gamma}2, fails to restore B cell maturation, despite supporting BAFF-dependent survival. Therefore, our data suggest that the BAFF-R–mediated survival signal, provided by PLC-{gamma}2, is not sufficient to promote B cell maturation, and that, in addition, activation of PLC-{gamma}2 by BCR is required for B cell development.

Key Words: cell differentiation • cell survival • B lymphocyte subsets • spleen • tumor necrosis factor


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