The goal of this project is to study the function and biology of haptenspecific murine B lymphocytes, using cloned lines of such cells generated by selective transformation with a hapten-modified transforming virus. Preliminary experiments have shown that liknes of 2, 4, 6-trinitrophenol (TNP)-binding B lymphocytes can be generated by transforming BALB/c splenocytes, enriched for TNP-specific B cells, with TNP-modified Epstein-Barr virus (EBV) but not unhaptenated EBV (which is tropic for primate B cells only). Subsequent studies will be done along the following lines. 1. This technique will be optimized and used to generate stable, cloned B cell lines that are: i) reactive with different haptens (e.g. TNP, fluorescein and haptens which induce immune responses with dominant idiotypes), and ii) derived from different B cells (e.g., folowing immunization with TD and TI antigens, and from mice with genetic disorders such as the xid defect and autoimmunity). 2. The phenotypic characteristics of hapten-EBV transformed lines wil be analyzed, with particular reference to the expression of hapten-specific immunoglobulines (Ig), viral antigens and DNA, and B cell differentiation markers. The goal is to correlate the phenotype of each line with its function and with the source of B cells. 3. The ability of hapten-specific clones to present haptenated and unmodi- fied protein antigens to IL-2 producing, antigen-reactive, Ia-restricted T cell hybridomas will be studied, with emphasis on the role of Ig receptors in this form of T-B interaction. Such a technique for generating antigen- presenting cloned B cell lines will be useful for analyzing mechanisms of antigen presentation and T cell activation. 4. The differentiation of hapten-specific B cell clones by antigens, helper T lymphocytes and polyclonal activators will be examined, particu- larly to analyze genetically restricted interactions between clonal popula- tions of B, T and antigen-presenting cells, and the roles of lymphokines and monokines. Finally, the effects of tolerogenic antigens, suppressor T cells and idiotypic signals on the growth and function of B cell clones will be studied.
| Lichtman, A H; Williams, M E; Ohara, J et al. (1987) Retrovirus infection alters growth factor responses of T lymphocytes. J Immunol 138:3276-83 |
| Lichtman, A H; Kurt-Jones, E A; Abbas, A K (1987) B-cell stimulatory factor 1 and not interleukin 2 is the autocrine growth factor for some helper T lymphocytes. Proc Natl Acad Sci U S A 84:824-7 |
| Lichtman, A H; Reynolds, D S; Faller, D V et al. (1986) Mature murine B lymphocytes immortalized by Kirsten sarcoma virus. Nature 324:489-91 |
