Signal Transduction by Immunoglobulin Is Mediated

Immunoglobulin (Ig) antigen receptors are composed of a noncovalently-associated complex of Ig and two other proteins, Igo~ and Ig3. The cytoplasmic domain of both of these Ig associated proteins contains a consensus sequence that is shared with the signaling proteins of the T cell and Fc receptor. To test the idea that Igc~-IgB heterodimers are the signaling components of the Ig receptor, we have studied Ig mutations that interfere with signal transduction. We find that specific mutations in the transmembrane domain of Ig that inactivate Ca 2+ and phosphorylation responses also uncouple IgM from Igoe-Ig/3. These results define amino acid residues that are essential for the assembly of the Ig receptor. Further, receptor activity can be fully reconstituted in Ca 2+ flux and phosphorylation assays by fusing the cytoplasmic domain of Igct with the mutant Igs. In contrast, fusion of the cytoplasmic domain of Ig~ to the inactive Ig reconstitutes only Ca z+ responses. Thus, Igor and IgB are both necessary and sufficient to mediate signal transduction by the Ig receptor in B cells. In addition, our results suggest that IgoL and IgB can activate different signaling pathways.