PRODUCTIVE INFECTION OF NORMAL CD40-ACTIVATED HUMAN B-LYMPHOCYTES BY HIV-1

Objective: Antigen-driven B-cell proliferation and maturation occur in germinal centres present in lymphoid tissues. This process is highly dependent on functional interactions between B and T lymphocytes. In v itro activation of CD40 present on B cells mimics B cell-T cell intera ctions and allows the proliferation of normal Epstein-Barr virus (EBV) -negative B lymphocytes. In HIV-1-seropositive individuals, B cells be come exposed to free viral particles and to infected T lymphocytes whi le migrating through germinal centres. The effect of HIV-1 viral expos ure on CD40-activated B lymphocytes was therefore examined. Methods: F reshly isolated B lymphocytes were cultured in vitro through activatio n of CD40. B-cell proliferation, HIV-1 infectivity and viral productio n were monitored following B-lymphocyte exposure to HIV-1. In addition , HIV-mediated fusion between infected B cells and uninfected CD4+ T l ymphocytes was assessed in a coculture assay. Results: EBV-negative, C D40-activated human B lymphocytes were directly infected by HIV-1. The infection significantly reduced their proliferation rate. Viral produ ction was detected in B-cell culture supernatant. Numerous fusion even ts indicated that HIV-1 infection of B lymphocytes could spread to T l ymphocytes following HIV-1-mediated fusion of these two cell types. Co nclusion: In view of the importance of B cell-T cell interactions in t he maintenance of a functional immune system, disruption of B-lymphocy te development could have direct implications on the course of AIDS pr ogression.