Coupling between B cell receptor and phospholipase C-gamma2 is essential for mature B cell development.
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)-gamma2 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-gamma2-/- mice is caused by a defect in either BCR or BAFF-R signaling. We find that a PLC-gamma2 SH2 mutant, which inhibits coupling between BCR and PLC-gamma2, 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-gamma2, is not sufficient to promote B cell maturation, and that, in addition, activation of PLC-gamma2 by BCR is required for B cell development.
Hikida
Masaki
M
Department of Molecular Genetics, Institute for Liver Research, Kansai Medical University, Moriguchi 570-8506, Japan.
Johmura
Sachiko
S
Hashimoto
Ari
A
Takezaki
Mayuko
M
Kurosaki
Tomohiro
T
D000818:Animals; D053265:B-Cell Activation Factor Receptor; D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D001854:Bone Marrow Cells / Q000502:physiology; D002470:Cell Survival; D019254:Genes, bcl-2; D008565:Membrane Proteins; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D016328:NF-kappa B / Q000378:metabolism; D051966:Phospholipase C gamma; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism*; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
D053265:B-Cell Activation Factor Receptor; D008565:Membrane Proteins; D016328:NF-kappa B; D011947:Receptors, Antigen, B-Cell; D018124:Receptors, Tumor Necrosis Factor; C486662:Tnfrsf13c protein, mouse; D010738:Type C Phospholipases; D051966:Phospholipase C gamma