Mechanism of B cell antigen receptor function: transmembrane signaling and triggering of apoptosis.
The antigen receptor of B lymphocytes (BCR) plays important roles in virtually every stage in the development, inactivation, or activation of B cells. The BCR is a complex of membrane immunoglobulin (mIg) and a heterodimer of two transmembrane polypeptides called Ig-alpha and Ig-beta. Site directed mutation of the mu immunoglobulin heavy chain has demonstrated that the mu transmembrane domain plays a key role in the assembly of mIgM with Ig-alpha/Ig-beta. In addition, there is a strong correlation between the ability of various mutant mIgM molecules to associate with Ig-alpha/Ig-beta and their ability to induce signal transduction reactions such as protein tyrosine phosphorylation and phosphoinositide breakdown. The cytoplasmic domains of Ig-alpha and Ig-beta share a region of limited homology with each other and with components of the T cell antigen receptor and of the Fc receptor. The presence of regions of the cytoplasmic domains of Ig-alpha or Ig-beta including this conserved amino acid sequence motif is sufficient to confer signaling function on chimeric transmembrane proteins. Both Ig-alpha and Ig-beta chimeras are capable of inducing all of the BCR signaling events tested. Based on these and related observations, we propose that the motifs act to initiate the BCR signaling reactions by binding and activating tyrosine kinases. Among the important events mediated by BCR signaling is induced expression of a series of genes referred to as early response genes. In B cells these include transcription factors and at least one component that regulates signaling events. One of these genes, c-myc, appears to play an important role in mediating apoptosis in B cells stimulated via the BCR complex.
DeFranco
A L
AL
Department of Microbiology & Immunology, University of California, San Francisco.
Mittelstadt
P R
PR
Blum
J H
JH
Stevens
T L
TL
Law
D A
DA
Chan
V W
VW
Foy
S P
SP
Datta
S K
SK
Matsuuchi
L
L
D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001665:Binding Sites; D017124:Conserved Sequence; D051379:Mice; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D011947:Receptors, Antigen, B-Cell