Engagement of the human pre-B cell receptor generates a lipid raft-dependent calcium signaling complex.
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.
Guo
B
B
The Molecular Biology Institute, University of California, Los Angeles 90095, USA.
Kato
R M
RM
Garcia-Lloret
M
M
Wahl
M I
MI
Rawlings
D J
DJ
D001402:B-Lymphocytes / Q000166:cytology / Q000502:physiology*; D002118:Calcium / Q000502:physiology*; D002460:Cell Line; D019070:Cell Lineage / Q000502:physiology*; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000502:physiology; D008055:Lipids / Q000502:physiology; D008562:Membrane Glycoproteins / Q000502:physiology*; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D015398:Signal Transduction / Q000502:physiology*
D007147:Immunoglobulin Light Chains; D008055:Lipids; D008562:Membrane Glycoproteins; D054420:Pre-B Cell Receptors; D011947:Receptors, Antigen, B-Cell; D002118:Calcium