Coupling between B cell receptor and phospholipase C-gamma2 is essential for mature B cell development

J Exp Med. 2003 Aug 18;198(4):581-9. doi: 10.1084/jem.20030280. Epub 2003 Aug 11.

Abstract

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Cell Activation Factor Receptor
  • B-Lymphocytes / cytology
  • B-Lymphocytes / physiology*
  • Bone Marrow Cells / physiology
  • Cell Survival
  • Genes, bcl-2
  • Membrane Proteins*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • NF-kappa B / metabolism
  • Phospholipase C gamma
  • Receptors, Antigen, B-Cell / metabolism*
  • Receptors, Tumor Necrosis Factor / metabolism*
  • Signal Transduction / physiology
  • Spleen / cytology
  • Type C Phospholipases / genetics
  • Type C Phospholipases / metabolism*

Substances

  • B-Cell Activation Factor Receptor
  • Membrane Proteins
  • NF-kappa B
  • Receptors, Antigen, B-Cell
  • Receptors, Tumor Necrosis Factor
  • Tnfrsf13c protein, mouse
  • Type C Phospholipases
  • Phospholipase C gamma