Inhibition of normal B-cell function by human immunodeficiency virus envelope glycoprotein, gp120

Narendra Chirmule, Naoki Oyaizu, V. S. Kalyanaraman, Savita G Pahwa

Research output: Contribution to journalArticle

31 Citations (Scopus)

Abstract

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, paraformal-dehyde-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.

Original languageEnglish
Pages (from-to)1245-1254
Number of pages10
JournalBlood
Volume79
Issue number5
StatePublished - Mar 1 1992
Externally publishedYes

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T-cells
Viruses
Glycoproteins
B-Lymphocytes
Cells
HIV
T-Lymphocytes
Cell proliferation
Antigens
Cell Differentiation
Human Immunodeficiency Virus env Gene Products
Cell Proliferation
Virus Diseases
Immunoglobulin G
Cytokines
CD4 Antigens
Clone Cells
Hypergammaglobulinemia
Cell culture
Interleukin-4

ASJC Scopus subject areas

  • Hematology

Cite this

Inhibition of normal B-cell function by human immunodeficiency virus envelope glycoprotein, gp120. / Chirmule, Narendra; Oyaizu, Naoki; Kalyanaraman, V. S.; Pahwa, Savita G.

In: Blood, Vol. 79, No. 5, 01.03.1992, p. 1245-1254.

Research output: Contribution to journalArticle

Chirmule, N, Oyaizu, N, Kalyanaraman, VS & Pahwa, SG 1992, 'Inhibition of normal B-cell function by human immunodeficiency virus envelope glycoprotein, gp120', Blood, vol. 79, no. 5, pp. 1245-1254.
Chirmule, Narendra ; Oyaizu, Naoki ; Kalyanaraman, V. S. ; Pahwa, Savita G. / Inhibition of normal B-cell function by human immunodeficiency virus envelope glycoprotein, gp120. In: Blood. 1992 ; Vol. 79, No. 5. pp. 1245-1254.
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