Research is divided into studies concerning the regulation of i) humoral immune responses to HIV-1 envelope glycoproteins, ii) virus replication in murine models of AIDS and iii) B cell activation in retrovirus- induced and autoimmune diseases. i) Serum and cells were obtained from mice and humans immunized with purified recombinant envelope glycoproteins from a variety of HIV-1 isolates in order to determine the number, specificity and cross- reactivity of B cells producing anti- bodies against gp120. Results indicate that the preferential expansion of B cells which cross- reactively recognized multiple HIV strains can be achieved by sequen- tially immunizing mice with different gp120 isolates. Glycosylated gp120 was found to act as a more efficient immunogen than non- glycosylated envelope glycoprotein or V3 look-region specific peptides. ii) Two murine models of HIV infection are being examined. In the murine AIDS model, levels of T cell activation and lymphokine production are being studied at the single cell level. In transgenic mice expressing gp120 proteins from HIV, the effect of immunization on tolerance and disease progression has been investigated. We are also studying SCID mice reconstituted with human PBL from gp160 vaccinated normal volunteers to analyze the degree of protection conferred by various immuni- zation regimens. An outgrowth of this work has been our finding that anti-HIV reactive cells are present initially in the peripheral cirulation and then home to the bone marrow of immunized donors. iii) We have been studying the number and antigenic specificity of lymphocytes secreting specific antibodies and lymphokines in patients and mice with SLE and AIDS. Results indicate that two processes - polyclonal activation and (auto) antigen specific immune stimulation - combine to induce the humoral abnormalities found in disease states. Murine models of these diseases are being used to analyze the specificity and cross-reactivity of activated B cells. This work is also providing considerable insight into the degree to which HIV-1 specific B cells are activated in patients with ARC and AIDS.
