Journal of virology 2017 05 03() pii 10.1128/JVI.00497-17
The maturation process of high-affinity antibodies is a result of intricate interactions between B cells and follicular helper T (Tfh) cells occurring in lymphoid germinal centers. HIV infection induces significant chronic immune activation, phenotypic skewing, and inflammation driven by years of continuous viral replication. High levels of viremia as well as immune activation and dysfunction have been demonstrated to have a perturbing impact on the B cell memory compartment and contribute to B cell exhaustion. Counterintuitively, the same factors associated with perturbation of the B cell compartment seem to be favorable factors for the generation of highly affinity matured Env-specific antibodies in a minority of HIV-infected individuals. Thus, understanding the impact of HIV antigenemia on B cells and Tfh cell interactions warrant further exploration. We therefore studied immunophenotypes of HIV-specific B cells in individuals with differing levels of viral control using HIV Env gp120-probes and characterized the functionality of matched T cells in peripheral blood. While CXCR5+CD4+ T cells were significantly diminished in HIV progressors, we found that a small subset of gp120-specific IL-21-secreting CXCR5+CD4 T cells were significantly associated with gp120-specific B cell frequencies. In contrast, neither bulk CXCR5+CD4 T cells nor other HIV antigen specificities were associated with gp120-specific B cell levels. HIV-specific B cells derived from elite controllers displayed greater amounts of gp120-specific B cells in the resting-memory subset whereas HIV-specific B cells in progressors accumulated in tissue-like and activated memory subsets. Furthermore, elite controller-derived CXCR5+CD4 T cells showed a stronger ex vivo capacity to induce B cell maturation and immunoglobulin class switching compared to HIV progressors.IMPORTANCE Dissecting the factors that are involved in B cell maturation and antibody development is important to understand for HIV vaccine design. Here we found that HIV Env-specific CXCR5+ CD4+T cells that are secreting Interleukin-21 are strongly associated with B cell memory phenotypes and function. Moreover, we found that the immune responses of HIV controllers showed intrinsically better helper activity than HIV progressors.