The investigators will study the role of membrane Ig and the function of helper T cells in the antibody response by exploiting a new, murine, in vitro polyclonal model for T cell/B cell cooperation. In this model, rabbit antibody against mouse immunoglobulin (anti-Ig) is used in place of antigen, and T cell help is provided by cultured T cell lines and cloned T cell hybridomas which recognize the rabbit anti-Ig reagents as foreign protein antigens. The investigators have shown that normal, small B cells act as extraordinarily efficient antigen presenting cells for rabbit anti-IgM or anti-IgD. Recognition of anti-Ig on the B cell surface is restricted by class II products of the major histocompatibility complex (MHC), and results in both a T cell response and a vigorous polyclonal B cell response. The model will be used to define the role of membrane Ig in antigen processing (if processing occurs in small B cells) and presentation of specifically bound antigen to helper T cells. Functional heterogeneity of helper T cells in their ability to interact with small B cells or other antigen presenting cells will be defined and explored. The mechanism of delivery of T cell help will be studied to determine whether help can be accounted for by secretion of characterized or novel lymphokines, or requires an early, contact-mediated event involving stimulated secretion of preformed mediators or interaction of membrane- bound molecules other then those required for specific recognition by the T cell. Finally, in an attempt to relate immune cell physiology to the cellular machinery which regulates cell division, the investigators have begun to study the effects of agents which activate B lymphocytes to different extents or by different pathways on the levels of cmyc mRNA in the cell during the first hours of the activation sequence. These studies will be extended to other cellular protooncogenes (c-fos, c-myb, c-ras) and genes induced by growth signals in fibroblasts (JE and KC), and transcription rates will be compared with mRNA levels.
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