Functional B cell abnormalities in HIV type 1 infection: role of CD40L and CD70

Early in HIV-1 infection, B cell responses to T cell-dependent antigens are impaired. In addition to the receptor-ligand pair CD40/CD40L, CD27/CD70 also appears to be involved in T cell-dependent B cell stimulation. We have shown that CD70+ B cells are the main producers of Ig when stimulated in a T cell-dependent manner, and that CD70 upregulation is dependent on interaction of CD40L on T cells with CD40 on B cells. We confirm here that B cells from HIV-infected individuals are impaired in T cell-dependent Ig production in vitro. This dysfunction could partly be restored by adding allogeneic T cells to the culture. In contrast, IgG production induced by CD40 MAb, IgM MAb, and IL-10 was in the normal range. In line with this, CD70 upregulation on B cells from HIV-infected individuals was impaired after stimulation in vitro by activated T cells but not after stimulation with CD40 MAb and IgM MAb. Furthermore, CD40L expression was decreased on CD4+ T cells after stimulation in vitro. Finally, CD70 expression on freshly isolated B cells from HIV-infected individuals was decreased, and low CD70 expression correlated with low IgG production after T cell-dependent stimulation. In conclusion, our data strongly suggest that impaired B cell responses to T cell-dependent Ag in HIV-1 infection are due to a defect in T cells.