Tumor necrosis factor-alpha inhibits the competence signal delivered by HIV to normal B cells.

Abstract

Polyclonal B cell activation is commonly observed in HIV-infected patients. The coordinate delivery of a number of signals is required for B cell response. This work was designed to better define the role of HIV in the first steps of normal human B cells activation. We show that the infectious virus or recombinant envelope proteins can render B cells responsive to the growth-promoting effect of several T cell-derived IL, IL-2, IL-4, and low m.w. (12-kDa) BCGF. HIV acts in the absence of monocytes and on different populations of B cells. The competence signal can be provided by recombinant gp160 envelope protein. CD4 molecule is not involved in the interaction of HIV with B cells. In addition, we demonstrate that tumor necrosis factor alpha has no promoting activity when B cells are preactivated by HIV and it can suppress the response of HIV-preactivated B cells to IL-2, IL-4, and 12-kDa BCGF. Thus, the HIV envelope can deliver an early signal to normal B cells and modulate B cell response to physiologic signals. The possible relevance of this phenomenon to the immune defect observed in HIV patients is discussed.