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Inhibition of normal B-cell function by human immunodeficiency virus
envelope glycoprotein, gp120
N Chirmule, N Oyaizu, VS Kalyanaraman and S Pahwa
Department of Pediatrics, North Shore University Hospital-Cornell
University Medical College, Manhasset, NY 11030.
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.
Volume 79,
Issue 5,
pp. 1245-1254,
03/01/1992
Copyright © 1992 by The American Society of Hematology
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