Regulation of B cell development by PLC-g2
Kansai Medical University and RIKEN Research Center for Allegy and Immunology, Moriguchi, Osaka, Japan
Antigen receptors on B lymphocytes (BCRs) play a central role in immune regulation by transmitting signals that regulate B lymphocyte survival, growth, and differentiation. Among a number of signaling pathways, the importance of phospholipase C (PLC)-g2 pathway has been underscored by gene targeting experiments in mice. PLC-g2-/- mice show reduced numbers of mature B2 B cells and poor antibody responses to T-independent type II antigens such as NP-Ficoll. Two signaling pathways known to be essential for progression from immature to mature B2 B cells are BAFF receptor (BAFF-R) and the BCR. Since PLC-g2 is required for a BAFF-R–mediated survival signal, we have examined the question of whether the reduced number of mature B2 B cells in PLC-g2-/- mice is caused by a defect in either BCR or BAFF-R signaling. We find that a PLC-g2 SH2 mutant, which inhibits coupling between BCR and PLC-g2, 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-g2, is not sufficient to promote B cell maturation, and that, in addition, activation of PLC-g2 by BCR is required for B cell development.
Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Nice, France; February 7 - 10, 2004; in oral session 1091 (Immunobiology).