Human B cells play a central role in the humoral immune response. Antigen dependent activation and clonal proliferation appear to proceed the B cell maturation into an antibody secreting plasma cells. The proliferation of activated B cell is controlled by an antigen independent and genetically unrestricted factor called B cell growth factor (BCGF). The mode of action, including any cofactor(s) requirement, and mechanism of release of this factor are completely illusive. It is important from immunological as well as the biological view point to understand the regulation of B cell proliferation at the molecular level. Two forms of BCGF have been defined by functional activity and source. We have detected a high mw intracellular (IC) BCGF in the cytoplasmic extract of lectin activated human PBLs, which release a low mw extracellular (EC) BCGF in the culture supernatants. We also found that the size of mRNA 16S coding for BCGF is such that it could translate into a protein of mw greater than 60 kd. Therefore, we have proposed that EC-BCGF is derived from a high mw precursor protein by post-translational cleavage.
Specific aims of this proposal is to verify this hypothesis. To this end it is planned (1) to demonstrate whether or not a correlation exists between the kinetics of biosynthesis of intracellular high mw BCGF and the release of low mw EC-BCGF. (2) To determine the biological relevance of IC-BCGF and compare it with that of EC-BCGF. (3) To demonstrate whether the hetrotypic goat anti-IC BCGF can cross react with the low EC-BCGF. (4) To show whether both high and low mw BCGF's can recognize the same BCGF receptor.
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