B Cell Antigen Receptor Ligation Activates a Receptor Associated Protein Tyrosine Kinase

Abstract

Blymphocytes express cell surface antigen receptors which function in antigen uptake for subsequent presentation to T cells, and in signal transduction leading to cell activation. The receptor is hetero- oligomeric, being composed of a membrane immunoglobulin molecule noncovalently associated with disulfide linked heterodimers of Ig-α and Ig-β or Ig-γ (for review see Cambier and Campbell in press) These subunits are encoded by mb-1 (Ig-α) and B29 (Ig-c and Ig-γ) genes, and function in signal transduction and receptor transport to the cell surface. Ig-α/β and -α/γ complexes have significant cytoplasmic structure which appears to act as a docking site for cytoplasmic enzymes involved in signal propagation. The enzymes include members of the src family of tyrosine kinases, phosphatidylinositol-3 kinase and other as yet unidentified molecules of 40, 42 and 38 kDa Mr (Cambier and Campbell in press; Clark et al in press). Studies utilizing fusion proteins containing Ig- α and Ig-β cytoplasmic tail sequences indicate that these proteins bind to a ~17 amino acid motif designated ARH1 (Clark et al in press). This motif, when derivated from TCRζ and CD3e chains, has been shown to contain all structural information necessary for signal transduction. The B cell antigen receptor complex is also associated with the syk tyrosine kinase, apparently via direct interaction with the mlgM heavy chain (μ). Thus available evidence indicates that multiple tyrosine kinases associate with the antigen receptor. The dynamics of this receptor-kinase association and kinase activation following antigen receptor crosslinking is not well defined.