Characterization of components of the murine B cell receptor complex and their role in anti-Ig stimulation.

Signal transduction in B cells is mediated by B cell receptor (BCR) complexes that are composed of membrane immunoglobulins (mIg) and additional proteins (e.g. Ig-alpha and Ig-beta) that have been implicated with several aspects of B cell activation. In this paper, experiments are described that have been designed to characterize new components of the BCR and to elucidate their involvement in B cell activation directly after the binding of anti-Ig. The data obtained prove the assumption that IgM is degraded after internalization. Neither immunoglobulin nor the Ig-alpha/beta heterodimer are re-expressed after they have disappeared from the cell surface. The newly detected Ig-alpha associated proteins are neither degradation products of immunoglobulins nor different forms of Ig-alpha or Ig-beta. In addition, they are not recognized by antibodies against any of the kinases known to date. The mIg molecules are linked to the cytoskeleton and internalized. On the other hand, the additional Ig-alpha associated proteins as well as the Ig-alpha/beta heterodimer could not be detected in the detergent-insoluble fraction. The former molecules remain on the B cell surface where they are attached to the unaffected isotype and might interact with downstream members of the signalling cascade. In addition, evidence is presented that the internalization of the receptor complex is not necessary for signal transduction and B cell activation. From these results the authors conclude that the BCR complexes are removed from the cell surface after binding of ligands, probably to prevent further activation of this cell, while the Ig-alpha associated proteins interact with the intracellular components of the signal transduction pathway to promote the further activation of the B cells.