Research is divided into studies concerning the regulation of i)humoral immune responses to HIV-1 envelop glycoproteins, ii) virus replication in murine AIDS and iii) B cell activation in retrovirus-induced and autoimmune diseases. i) Mice were 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 antibodies against gp120. Results indicate that the preferential expansion of B cells which cross-reactively recognized multiple HIV strains can be achieved by sequentially immunizing mice with different gp120 isolates. Glycosylated gp120 was found to act as a more efficient immunogen than non-glycosylated envelope glycoprotein. ii) The Murine AIDS model is being used to study a) the efficacuy of X- irradiation and bone marrow reconstitution combined with AZT therapy on disease progression and b) the susceptibility of MAIDS mice to develop autoimmune-mediated cardiomyopathy following secondary infection with Coxsackie B Virus. We are also utilizing SCID mice reconstituted with human PBL from gp160 vaccinated normal volunteers to analyze the degree of protection conferred by various immunization regimens. An outgrowth of this work has been our finding that anti-HIV reactive cells are present initially in the peripheral circulation and then home to the bone marrow of immunized donors. iii) We have been studying the number and antigenic specificity of B cells secreting Ig in patients 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 anaylze the specificity and cross-reactivity of acti- vated 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.
