Membrane immunoglobulin and its accomplices: new lessons from an old receptor.
B lymphocytes express multisubunit receptors for antigen that play multiple roles in generation of the immune response. These receptors act as transmembrane signal transducers but also act to capture, concentrate, and internalize antigen for subsequent proteolytic processing and presentation to T cells. During the past decade great progress has been made in our understanding of the extended structure of the receptor and the molecular basis by which it transduces signals. It is now clear that the B cell antigen receptor is a complex structure composed of antigen binding and transducer/transporter substructures. The antigen binding substructure is composed of disulfide-linked immunoglobulin H and L chains, and is noncovalently associated with transducer/transporter substructures composed of disulfide-linked heterodimers of alpha, beta, and gamma chain products of the mb-1 (alpha) and B29 (beta and gamma) genes. The cytoplasmic tails of these chains associate with src-family tyrosine kinases including fyn, lyn, blk, and lck and other SH2-containing molecules such as phosphatidylinositol 3-kinase. Available evidence indicates that these interactions are mediated via an amino acid sequence motif of approximately 22 amino acids that is found in both alpha and beta chains. Receptor ligation triggers the activation of multiple receptor-associated src-family kinases leading to phosphorylation and activation of PLC gamma 1 and PLC gamma 2. Subsequent phosphoinositide hydrolysis and calcium mobilization, presumably acting in concert with other tyrosine kinase-activated mechanisms, leads to transcriptional activation of a number of immediate early genes and, ultimately, to B cell proliferation.
Cambier
J C
JC
Department of Pediatrics, National Jewish Center for Immunology and Respiratory Medicine, Denver, Colorado.
Campbell
K S
KS
D000595:Amino Acid Sequence; D000818:Animals; D002462:Cell Membrane / Q000378:metabolism; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism*; D008969:Molecular Sequence Data; D011947:Receptors, Antigen, B-Cell / Q000737:chemistry / Q000502:physiology; D015398:Signal Transduction
D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell