We wish to understand the control of normal and neoplastic B cell growth and differentiation by analyzing hapten-purified B lymphocytes and specific lymphomas or lymphoma-hybridomas. Hapten-specific B cells will be isolated from FL-gelatin plates and grown in agar as colony forming B cells (CFU-B) to follw the development of normal and """"""""tolerant"""""""" B cells. Such progeny colonies can be directly assayed for antibody secretion or isolated and challenged with antigen or B cell stimulatory factors such as BCGF, BCDF, etc. This approach allows the expansion of single, specific B cell subsets for analysis of growth and differentiation, as well as for the establishment of long term lines or transformants. These cells will be characterized for surface phenotype, responsiveness to factors, tolerogen, and these parameters correlated with well characterized B lymphoma lines. Such studies in conjunction with cell cycle analyses will establish the molecular events and defects in signal transmission in B cell activation and unresponsiveness. We will also compare these lines with lymphomas of known specificity and differentiative capacity and with specific hybridomas constructed with hapten-purified B cells and model lymphomas, as well as B lymphocytes transformed by EBV via a novel procedure. These studies will provide an understanding of the molecular and cell surface events in the regulation and growth and differentiation of both normal and transformed lymphocytes, as well as malignant lymphoma cells.
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