Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta

doi:10.1084/jem.178.3.1049

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Signal transduction by immunoglobulin is mediated through Ig alpha and Ig beta

M Sanchez, Z Misulovin, AL Burkhardt, S Mahajan, T Costa, R Franke, JB Bolen and M Nussenzweig
Howard Hughes Medical Institute, Rockefeller University, New York, NY 10021.

Immunoglobulin (Ig) antigen receptors are composed of a noncovalently- associated complex of Ig and two other proteins, Ig alpha and Ig beta. 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 Ig alpha-Ig beta 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 Ca2+ and phosphorylation responses also uncouple IgM from Ig alpha-Ig beta. These results define amino acid residues that are essential for the assembly of the Ig receptor. Further, receptor activity can be fully reconstituted in Ca2+ flux and phosphorylation assays by fusing the cytoplasmic domain of Ig alpha with the mutant Igs. In contrast, fusion of the cytoplasmic domain of Ig beta to the inactive Ig reconstitutes only Ca2+ responses. Thus, Ig alpha and Ig beta are both necessary and sufficient to mediate signal transduction by the Ig receptor in B cells. In addition, our results suggest that Ig alpha and Ig beta can activate different signaling pathways.
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