Signal transduction by the B-cell antigen receptor.
The antigen receptor of B lymphocytes (BCR) plays important roles in recognition of foreign antigens and self-components to allow the immune system to make appropriate antibody responses. The BCR is a complex between membrane immunoglobulin and the Ig-alpha and Ig-beta heterodimer. Site-directed mutagenesis experiments have shown that the mu heavy chain transmembrane domain plays a key role in the association of mIgM with Ig-alpha/Ig-beta. In the absence of complex formation, mIgM is retained in the endoplasmic reticulum, and this function is also specified by the mu chain transmembrane domain. The ability of various mutant mIgM molecules to associate with Ig-alpha/Ig-beta correlates well with their ability to induce signal transduction reactions such as protein tyrosine phosphorylation and phosphoinositide breakdown. Thus, the signaling ability of the BCR appears to reside in the Ig-alpha/Ig-beta heterodimer. The cytoplasmic domains of Ig-alpha and Ig-beta each contain an ITAM sequence, which is defined by its limited homology with subunits of the T-cell antigen receptor and of Fc receptors. Moreover, chimeric proteins containing these ITAMs and surrounding sequences from the cytoplasmic domains of Ig-alpha or Ig-beta exhibit signaling function characteristics of the intact BCR. The Ig-alpha and Ig-beta chimeras are each capable of inducing all of the BCR signaling events tested and thus represent redundant functions. Cross-linking these chimeras leads to their phosphorylation and to binding of the intracellular tyrosine kinases Lyn and Syk. The BCR expressed in the nonlymphoid AtT20 cells, which express the Src-family tyrosine kinase Fyn but not Syk, was not able to trigger vigorous signaling reactions. Introduction of the active form of Syk into these cells restored some signaling events. These results are consistent with a model in which the ITAMs act to initiate the BCR signaling reactions by binding and activating tyrosine kinases.
D000818:Animals; D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D002462:Cell Membrane / Q000276:immunology / Q000502:physiology; D003593:Cytoplasm / Q000276:immunology; D006801:Humans; D046911:Macromolecular Substances; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011948:Receptors, Antigen, T-Cell / Q000502:physiology*; D015398:Signal Transduction / Q000276:immunology*
D000941:Antigens; D046911:Macromolecular Substances; D011947:Receptors, Antigen, B-Cell; D011948:Receptors, Antigen, T-Cell