Recent reports that HIV-1 can influence B cell activation, proliferation and differentiation which are also known to be regulated by various lymphokines, raise the possibility that HIV-1 transmits signals lymphokine-induced B cell growth. This, combined with other reports that B cells express lymphokine receptors and secrete their own lymphokines, prompted us to establish the following model: HIV-1 exerts its direct effect on B cells via interactions with unique B lymphokine receptors; this is followed by secretion of B lymphokines which are autoutilized by the cells for growth and differentiation. The B cell lymphokines may also influence T cell activation and upregulate HIV-1 expression in CD4+ T cells. To test this hypothesis, tumor B cell lines derived from patients with AIDS and Burkitt's lymphoma and normal lymphoblastoid EBV-transformed B cell lines are studied for lymphokine secretion and lymphokine receptor expression. Lymphokine reactivities in these AIDS-associated B cell lines (AABCL) will be compared to those of other B cell lines (non-AABCL). If distinct lymphokine receptors or secreted lymphokines are identified, they will be studied at the molecular level; this will include purification of the receptors and amino acid sequencing of the secreted lymphokines. Subsequently, by using synthetic peptides which correspond to different regions of the viral envelope we will try to delineate whether HIV-1 binds to these lymphokine receptors. The possible combined role of HIV-1 and EBV in B cell lymphokine modulation will be studied as well. The second part of the project concentrates on the effects of these B lymphokines on B cell and T cell immunoregulation and HIV-1 expression. The data obtained from this project might: (i) contribute to identification of novel lymphokines and receptors modified by HIV-l/EBV; (ii) elucidate possible mechanism HIV-1 binding to B cells: (iii) shed new light on polyclonal B cell activation in AIDS patients, and explain why and how, B cells """"""""escape"""""""" HIV- 1 cytopathic effects; (iv) demonstrate that B cell lymphokines increase T cell susceptibility to HIV-1; (v) bring new insights into HIV-1 persistence in the human host.
