John Cambier, National Jewish Medical and Research Center
Antigen receptors appear unique in biology in transducing signals with distinct biologic outcomes depending upon the affinity and valence of the antigen, and the differentiative stage of the responding cell. Thus it appears that the receptor is not a binary switch, but rather can somehow sense differences in antigen structure and affinity. Differentiative stage specific responses to antigen are apparently determined by alternative expression and usage of co-receptors, accessory molecules, and signaling intermediaries. The primary goal of our research is elucidation of the molecular circuitry involved in antigen receptor signal transduction. Ongoing studies address the function of specific sites within the receptors transducer subunit's cytoplasmic tails; the function of the accessory molecules CD45, CD19 and CD22 that modulate antigen receptor signaling; the molecular bases of alterations in signaling seen as B cells mature and differentiate into germinal center cells and memory cells; mechanisms by which receptor sensitivity to antigen is regulated; and use of Ig-a and Ig-b for signal transduction by other receptors, such as the Pre-B cell receptor and MHC class II molecules expressed on antigen stimulated B cells. Finally, our interests extend to mechanisms by which inhibitory co-receptors such as Fc$\gamma$RIIb function to modulate BCR signaling, diverting the cells response toward apoptosis. This presentation will focus on molecular circuitry in BCR signaling and its modulation by Fc$\gamma$RIIb.