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) co mplexes that are composed of membrane immunoglobulins (mig) and additi onal proteins (e.g. Ig-alpha and Ig-beta) that have been implicated wi th several aspects of B cell activation. In this paper, experiments ar e described that have been designed to characterize new components of the BCR and to elucidate their involvement in B cell activation direct ly after the binding of anti-Ig. The data obtained prove the assumptio n that IgM is degraded after internalization. Neither immunoglobulin n or the Ig-alpha/beta heterodimer are re-expressed after they have disa ppeared from the cell surface. The newly detected Ig-alpha ssociated p roteins are neither degradation products of immunoglobulins nor differ ent 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 molec ules are linked to the cytoskeleton and internalized. On the other han d, the additional Ig-alpha ssociated proteins as well as the Ig-alpha/ beta heterodimer could not be detected in the detergent-insoluble frac tion. 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 aut hors conclude that the BCR complexes are removed from the cell surface after binding of ligands, probably to prevent further activation of t his cell, while the Ig-alpha ssociated proteins interact with the intr acellular components of the signal transduction pathway to promote the further activation of the B cells.