Inhibition of normal B-cell function by human immunodeficiency virus envelope glycoprotein, gp120.
Despite the occurrence of hypergammaglobulinemia in human immunodeficiency virus (HIV) infection, specific antibody production and in vitro B-cell differentiation responses are frequently impaired. In this study, we have examined the effects of HIV envelope glycoprotein gp120 on T-helper cell function for B cells. In the culture system used, B-cell functional responses were dependent on T-B-cell contact, since separation of T and B cells in double chambers by Transwell membranes rendered the B cells unresponsive in assays of antigen-induced B-cell proliferation and differentiation. Cytokines secreted by T cells were also essential, since anti-CD3 monoclonal antibody (mAb)-activated, paraformaldehyde-fixed T-cell clones failed to induce B-cell proliferation and differentiation. Pretreatment of the CD4+ antigen-specific T cells with gp120 was found to impair their ability to help autologous B cells, as determined by B-cell proliferation, polyclonal IgG secretion, and antigen-specific IgG secretion. The gp120-induced inhibition was specific in that it was blocked by soluble CD4. Furthermore, only fractionated small B cells (which are T-cell-dependent in their function) manifested impaired responses when cultured with gp120-treated T cells. Antigen-induced interleukin (IL)-2 and IL-4, but not IL-6, secretion were markedly reduced in gp120-treated T-cell clones. Addition of exogenous cytokines failed to compensate for defective helper function of gp120-treated T cells. The findings in this study indicate that gp120 impairs helper functions of CD4+ T cells by interfering with T-B-cell contact-dependent interaction; the inhibitory effects of soluble envelope proteins of HIV may contribute to the immunopathogenesis of the HIV-associated disease manifestations.
Chirmule
N
N
Department of Pediatrics, North Shore University Hospital-Cornell University Medical College, Manhasset, NY 11030.
Oyaizu
N
N
Kalyanaraman
V S
VS
Pahwa
S
S
D000941:Antigens / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation; D002455:Cell Division; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism; D005404:Fixatives; D005557:Formaldehyde; D015699:HIV Envelope Protein gp120 / Q000502:physiology*; D006801:Humans; D008213:Lymphocyte Activation; D011108:Polymers; D006377:T-Lymphocytes, Helper-Inducer / Q000276:immunology; D013744:Tetanus Toxin / Q000276:immunology
D000941:Antigens; D016207:Cytokines; D005404:Fixatives; D015699:HIV Envelope Protein gp120; D011108:Polymers; D013744:Tetanus Toxin; D005557:Formaldehyde; C003043:paraform