gp120- and TNF-alpha-induced modulation of human B cell function: proliferation, cyclic AMP generation, Ig production, and B-cell receptor expression.
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.


CONCLUSIONS
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.
Patke
C L
CL
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.
Shearer
W T
WT
D000918:Antibody Specificity; D001402:B-Lymphocytes / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D002455:Cell Division; D000242:Cyclic AMP / Q000378:metabolism; D015699:HIV Envelope Protein gp120 / Q000276:immunology / Q000494:pharmacology*; D015497:HIV-1; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D011947:Receptors, Antigen, B-Cell / Q000096:biosynthesis; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015699:HIV Envelope Protein gp120; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell; D014409:Tumor Necrosis Factor-alpha; D000242:Cyclic AMP