Signaling-defective mutants of the B lymphocyte antigen receptor fail to associate with Ig-alpha and Ig-beta/gamma.

The B cell receptor for antigen, the membrane immunoglobulin (mIg) molecule, is normally expressed in association with at least two other proteins, mb-1 (Ig-alpha) and B29 (Ig-beta/gamma). We have previously described a set of murine B cell clones transfected with wild-type and mutated forms of membrane-bound IgM (mIgM) that vary in their ability to transduce signals to the cell interior. Analysis of the B cell receptor complex in signaling and nonsignaling mutants of mIgM reveals complete concordance between intact signaling ability and ability of the mIgM to associate with Ig-alpha and Ig-beta/gamma. These results point to the importance of the mIgM transmembrane region in mediating binding to accessory molecules, and provide support for a role of Ig-alpha and Ig-beta/gamma that extends beyond surface expression to signal transduction in B lymphocytes.