B-cell antigen receptor-induced apoptosis requires both Ig alpha and Ig beta.
The response of a B cell to antigen is dependent on the surface expression of a clonotypic B-cell receptor complex (BCR) consisting of membrane-bound Ig and disulfide-linked heterodimers of Ig alpha/beta. Studies of Ig alpha or Ig beta have shown that the immunoreceptor tyrosine-based activation motif (ITAM) found in each cytoplasmic tail is capable of inducing most receptor signaling events. However, Ig alpha, Ig beta, and most of the other receptor chains that contain ITAMs, including CD3 epsilon, CD3 gamma, TCR zeta, and Fc epsilon Rl gamma, are found as components of multimeric and heterogeneous complexes. In such a complex it is possible that cooperativity between individual chains imparts functional capacities to the intact receptor that are not predicted from the properties of its constituents. Therefore, we developed a novel system in which we could form and then aggregate dimers, representative of partial receptor complexes, which contained either Ig alpha alone, Ig beta alone, or the two chains together and then examine their ability to induce apoptosis in the immature B-cell line, WEHI-231. Here we present evidence that heterodimers of Ig alpha and Ig beta efficiently induced apoptosis while homodimers of either chain did not. Apoptosis was associated with the inductive tyrosine phosphorylation of a very restricted set of proteins including the tyrosine kinase Syk. These findings may provide insight into the mechanisms by which the BCR, and other such multimeric receptor complexes, initiate both apoptotic and proliferative responses to antigen.
Tseng
J
J
Department of Medicine, University of Chicago, IL 60637, USA.
Eisfelder
B J
BJ
Clark
M R
MR
D015703:Antigens, CD / Q000276:immunology*; D017209:Apoptosis / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology / Q000473:pathology*; D051925:CD79 Antigens; D018076:DNA, Complementary / Q000235:genetics; D006801:Humans; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D011947:Receptors, Antigen, B-Cell / Q000235:genetics / Q000276:immunology*; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000276:immunology; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000276:immunology; D015398:Signal Transduction / Q000276:immunology; D014407:Tumor Cells, Cultured
D015703:Antigens, CD; D051925:CD79 Antigens; C497881:CD79A protein, human; D018076:DNA, Complementary; D011947:Receptors, Antigen, B-Cell; D011993:Recombinant Fusion Proteins; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; D017479:Receptors, Platelet-Derived Growth Factor