C L Patke1, W T Shearer. 1. Departments of Pediatrics and Microbiology and Immunology, Baylor College of Medicine, and the Department of Allergy and Immunology, Texas Children's Hospital, Houston, TX 77030, USA.
Abstract
BACKGROUND: It is well known that HIV-1 infection induces profound alterations in the immune system, including hyperactivation of B cells. TNF-alpha 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-alpha 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-alpha also stimulated cAMP generation, proliferation, and Ig production in B cells, and the binding of gp120 to these B cells stimulated by TNF-alpha 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-alpha. CONCLUSION: gp120 modulation of TNF-alpha-induced B-cell receptor- and cAMP-mediated signal transduction events may be involved in the B-cell abnormalities observed in HIV-1 infection.
BACKGROUND: It is well known that HIV-1 infection induces profound alterations in the immune system, including hyperactivation of B cells. TNF-alpha 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-alpha 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-alpha also stimulated cAMP generation, proliferation, and Ig production in B cells, and the binding of gp120 to these B cells stimulated by TNF-alpha 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-alpha. CONCLUSION:gp120 modulation of TNF-alpha-induced B-cell receptor- and cAMP-mediated signal transduction events may be involved in the B-cell abnormalities observed in HIV-1 infection.
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