The regulation of proliferation and immunoglobulin secretion of B lymphocytes in response to antigen is controlled through the interaction with T lymphocytes and macrophages. This interaction leads to the production of several lymphokines among which are B cell growth factors. The objective of the proposed research is to clone cDNAs and genes for B cell growth factors (BCGF). Our work to date has established: a) two classes of BCGFs were distinguished due to their action at different points in the cell cyle of synchronized B cell blasts, b) sensitive assay for each BCGF have been developed which is crucial to the unequivocal identification of cDNA clones, c) T cell hybridomas which produce only one type of BCGF but not the other have been characterized, d) assays for the translation of mRNA into activity have been established, and e) sizes of mRNA species encoding for BCGFs have been elucidated. We propose to extend this study to determine the DNA sequences and gene structure of BCGFs by cDNA and genomic cloning. This will allow us to establish the relationship between the different BCGF proteins. Since the purification to homogeneity of individual BCGFs is extremely difficult due to the minute quantities produced by the cell lines available to date, the determination of their exact mode of action in the regulation of B lymphocyte proliferation has not yet been possible. Therefore, we propose to generate high yield sources of individual BCGFs by employing eucaryotic expression vectors. The elucidation of the number of individual BCGF proteins by isolating their cDNAs and the production of individual BCGFs in pure form without the contamination of others will greatly facilitate the determination of their role in the proliferation of B lymphocytes. Availability of molecular probes for BCGFs will allow investigation into the possible aberrant expression of BCGF genes in B cells neplasms.
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