Mentored Scientist Award

HIV-1 induced B cell dysfunction typically presents as a loss of memory B cells and attenuated antibody responses, paradoxically with concomitant increases in activated B cells and hypergammaglobulinaemia. While some loss of functionality could be due to the loss T cell help, T cell triggering of inhibitory signaling pathways has also been implicated. Of these pathways, members of the TNF-receptor superfamily and subsequent downstream signaling events appear to have a prominent impact on regulating B cell function. signaling through CD40, a member of the TNF-receptor superfamily, is essential for class switching, memory B cell development and germinal center formation. CD30L (CD153), also a member of the TNF receptor superfamily, is expressed on B cells and has been shown to inhibit class switching and somatic hypermutation through the competitive inhibition of CD40 signaling molecules. We have recently described the increased expression of CD30 on a subset of CD4+ T cells in HIV-1 infected individuals.CD30/CD30L signaling is polyfunctional and differs depending on the cell type and other simultaneous co-signaling events. The effect of CD30L signaling in B cells in the setting of HIV-1 infection is entirely unknown. The purpose of this study is to characterize the effect of CD30/CD30L signaling on B cell function in the setting of HIV-1 infection, with a particular focus on B cell differentiation and antibody production. In addition, this study will also seek to clarify if CD30L signal inhibition is able to restore, at least in part, B cell function and antibody production.