Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex

Immunity. 2000 Aug;13(2):243-53. doi: 10.1016/s1074-7613(00)00024-8.

Abstract

Pre-B cell receptor (pre-BCR) expression is critical for B lineage development. The signaling events initiated by the pre-BCR, however, remain poorly defined. We demonstrate that lipid rafts are the major functional compartment for human pre-B cell activation. A fraction of pre-BCR was constitutively raft associated, and receptor engagement enhanced this association. These events promoted Lyn activation and Igbeta phosphorylation and led to the generation of a raft-associated signaling module composed of tyrosine phosphorylated Lyn, Syk, BLNK, PI3K, Btk, VAV, and PLCgamma2. Formation of this module was essential for pre-BCR calcium signaling. Together, these observations directly link the previously identified genetic requirement for the components of this module in B lineage development with theirfunctional role(s) in human preBCR signaling.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • B-Lymphocytes / cytology
  • B-Lymphocytes / physiology*
  • Calcium / physiology*
  • Cell Line
  • Cell Lineage / physiology*
  • Humans
  • Immunoglobulin Light Chains / physiology
  • Lipids / physiology
  • Membrane Glycoproteins / physiology*
  • Pre-B Cell Receptors
  • Receptors, Antigen, B-Cell
  • Signal Transduction / physiology*

Substances

  • Immunoglobulin Light Chains
  • Lipids
  • Membrane Glycoproteins
  • Pre-B Cell Receptors
  • Receptors, Antigen, B-Cell
  • Calcium