STRUCTURE/FUNCTION HUMAN B CELL DIFFERENTIATION ANTIGENS

本研究计划的主要目标是研究如何

The principal goal of this research proposal is to investigate how proliferation and differentiation of human B cells are regulated. A major focus will be on interactions occurring at the cell surface that involve B cell differentiation antigens. Our approach stems from our findings that monoclonal antibodies (mAb) to certain epitopes on certain B cell-associated antigens have agonistic activity: the mAb 1F5 to the 35Kd pan B cell marker Bp35 activates resting B cells to leave G0 and enter the G1 phase of the cell cycle. In contrast, the mAb G28-5 to the 50Kd pan B cell antigen Bp50 does not affect resting B cells, but like certain B cell growth factors (BCGF), stimulates activated B cells to traverse the cell cycle. Our rationale is that agonistic mAb provide an alternative and complementary approach to soluble factors for studying B cell immunoregulation. Our current hypothesis is that Bp35 and Bp50 are surface receptors for either soluble B cell stimulating factors (BSF) or for transmembrane cell-cell interaction signals from accessory cells. The specific aims of the proposal are: 1) to test whether Bp35 or Bp50 are receptors for known soluble BSF, 2) to assess the effects that anti-Bp35 and anti-Bp50 agonistic mAb have on growth factor regulation, 3) to characterize and contrast the intracellular pathways that are induced in B cells by agonistic mAb, and 4) to clone and isolate the gene which encodes for the Bp35 surface polypeptide. Further information about Bp35 and Bp50 structure and their role in B cell activation will contribute to our understanding of the etiology and possible control of lymphoid malignancies and antibody-mediated autoimmune diseases.