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 Igα/β. Studies of Igα or Igβ have shown that the immunoreceptor tyrosine-based activation motif (ITAM) found in each cytoplasmic tail is capable of inducing most receptor signaling events. However, Igα, Igβ, and most of the other receptor chains that contain ITAMs, including CD3ε, CD3γ, TCRζ, and FcεRIγ, are found as components of multimeric and heterogenous 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 Igα alone, Igβ 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 Igα and Igβ 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.
Anti-immunoglobulin-induced Apoptosis in WEHI 231 Cells Involves the Slow Formation of Ceramide from Sphingomyelin and Is Blocked by bcl-xL