Antigen-driven B-cell proliferation and maturation occur in germinal centers present in lymphoid tissues. This process is highly dependent on functional interactions between B and T lymphocytes. In vitro, activation of CD40 present on B cells mimics B cell-T cell interactions and allows the proliferation of normal EBV-negative B lymphocytes. In HIV-l-seropositive individuals, B cells become exposed to free viral particles and to infected T lymphocytes while migrating through germinal centers. To study the effect of HIV-1 exposure on the proliferation and maturation of B lymphocytes, HIV-1 was added to the culture of CD40 activated B cells. B lymphocytes got readily infected as demonstrated by PCR analysis of proviral DNA. These B cells were negative for CD4 cell surface expression. The infection was accompanied by a decrease in the proliferation rate of the cells. This decrease could not be attributed to a reduction of B cells expressing surface immunoglobulin molecules of the VH3
family. No cytopathic effect could be observed. Viral production was detected in B-cell culture supernatant. Numerous fusion events indicated that HIV-1 infection could spread to T lymphocytes following HIV-1 mediated fusion of these two cell types. In view of the importance of B cell-T cell interactions in the maintenance of a functional immune system, disruption of B-lymphocyte development could have direct implications on the course of AIDS progression.