The goal of this proposal is to study the control of antibody responses by regulatory T lymphocytes using purified and clonal B cell populations and a combination of molecular and cellular immunologic techniques. The project is divided into two components. 1. Mechanisms of action of suppressor T lymphocytes (Ts): Functional inhibition of mouse myeloma cells by syngeneic idiotype-specific Ts in vitro will be studied with particular emphasis on the following aspects. First, the nature of Ts-target interactions, specificities of Ts and their secreted mediator(s) and the role of non-lymphoid accessory cells in the effector phase of T cell-mediated suppression will be examined, using whole Ts, culture supernatants and hybridomas as sources of suppressor factors. Second, immunoglobulin (Ig) biosynthesis and mRNA will be analyzed in suppressed myeloma cells, to establish if Ts inhibit transcription of Ig heavy or light chain genes, translation of mRNA or post-synthetic modification of Ig polypeptides. Cell lines secreting two different antibodies will be constructed by somatic cell hybridization and gene transfection, to determine the selectivity of T cell-mediated suppression and whether expression of Ig heavy and light chains is regulated independently or co-ordinately. 2. Interactions between antigen-specific B and helper T lymphocytes: The bidirectional, antigen-specific interactions between purified hapten-binding B lymphocytes and cloned lines of carrier-reactive, Ia-restricted helper T cells will be examined in vitro. In particular, the ability of B cells to present antigens to an activate various naive and immune helper cell populations, including accessory factor (e.g. IL1)-dependent T cells, will be studied, and compared with """"""""conventional"""""""" antigen-presenting cells. The role of hapten-binding Ig receptors and antigen processing in this function of B cells will be examined. Mice with selective B cell deficiencies will be used to evaluate the importance of this cell type in initiating immune responses to conventional immunization with protein antigens. Finally, the effects of helper T cell activation on the growth and differentiation of antigen-presenting and bystander B lymphocytes will be analyzed, primarily to establish correlations between antigen presentation by and functional responses of B cells.
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