|Budget Amount *help
¥7,300,000 (Direct Cost : ¥7,300,000)
Fiscal Year 1994 : ¥2,200,000 (Direct Cost : ¥2,200,000)
Fiscal Year 1993 : ¥5,100,000 (Direct Cost : ¥5,100,000)
B cell antigent receptor is composed of antigen specific membrane IgM molecule and its associated proteins of MB-1 (Ig-alpha, CD79a) and B29 (Ig-beta, CD79b) .This basic structure is essential not only for the expression of B cell antigen receptor on the surface of B lymphocytes but also for signal transduction of stimulatory signal given by antigen. Within cytoplasmic domains of MB-1 and B29, there are antigen recognition consensus motif that can bind to various functional components related to the signal transduction. B cell antigen receptor complex involves src-type tyrosine kinase Lyn, Fyn, Lck, Blk, non src-tyupe tyrosine kinase Syk, and PI-3 kinase. Crosslinking of antigen receptor induces signal transduction of phosphatidyl inositol patyways, leading to the increase of intracellular Ca mobilization and protein kinase sctivity. It also induces signal transduction of ras-MECK/MAPK pathway leading to activation of nuclear transcription factors. Activation to antigen receptor on B cells also induces PI-3 kinase activity which then probably mediates important signal for the proliferation and differentiation of B cells.
Regardless of these fundamental findings concerning to B cell signal transduction pathways, little is known about the mechanism and quality of signal transduction through these signal transduction pathways in different stages of B lineage cells. To clearly identify novel molecules involved in the B cell antigen receptor complex, we searched for the functional phosphoprotein molecules associated with MB-1 protein. A 52 kDa protein is coprecipitated with anti-MB-1 protein. We prepared rat monoclonal antibody against this 52 kDa protein and isolated a candidate cDNA clone named alpha4 with this monoclonal antibody. The alpha4 cDNA clone is a new molecule which is tightly associated with kinase molecules in B cells, which is located in the down stream of the signal transduction through B cell antigen raceptor.