Gp120- and TNF-α–induced modulation of human B cell function: Proliferation, cyclic AMP generation, Ig production, and B-cell receptor expression

Abstract

Background: It is well known that HIV-1 infection induces profound alterations in the immune system, including hyperactivation of B cells. TNF-α induces HIV-1 replication and immunodysregulation, including polyclonal B-cell activation. Objective: We sought to determine the effects of surface-binding HIV-1 envelope glycoprotein (gp120) and TNF-α on human B-cell function. Methods: HIV-1 seronegative peripheral blood human B cells were purified and activated by CD40 mAb and IL-4. In vitro studies of B-cell proliferation, cyclic AMP (cAMP) generation, receptor expression, and Ig production were performed. Results: gp120, an Ig superantigen, stimulated HIV-1 seronegative and HIV-1 seropositive human B-cell cAMP generation, proliferation, and Ig production. These gp120-induced B-cell responses were demonstrated to be specific as evidenced by the abrogation of the stimulatory response in the presence of anti-gp120 mAb, blocking of CD4 resulting in no change on gp120-induced B-cell responses, and the binding of gp120 in these B cells. TNF-α also stimulated cAMP generation, proliferation, and Ig production in B cells, and the binding of gp120 to these B cells stimulated by TNF-α further enhanced cell proliferation, cAMP generation, and Ig production. Antigenic expression of the B-cell receptor CD79b was down-regulated by gp120 but was not altered by the addition of TNF-α. Conclusion: gp120 modulation of TNF-α–induced B-cell receptor- and cAMP-mediated signal transduction events may be involved in the B-cell abnormalities observed in HIV-1 infection. (J Allergy Clin Immunol 2000;105:975-82.)