Envelope glycoproteins of HIV-1 interfere with T-cell-dependent B cell differentiation: Role of CD4-MHC class II interaction in the effector phase of T cell help

Narendra Chirmule, Xue Ping Wang, Rong Hu, Naoki Oyaizu, Chaim Roifman, Rajendra Pahwa, Vaniambadi S. Kalyanaraman, Savita Pahwa

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

T-cell-dependent B cell differentiation involves two phases: an inductive phase of T cell activation followed by an effector phase, which involves stimulation of B cells by activated T cells. We have previously demonstrated that anti-CD3 mAb and antigen-induced T-cell-dependent B cell functions are inhibited by HIV-1 envelope glycoprotein, gp120, at the inductive phase of T-cell-dependent B cell response. In this study we have investigated whether gpl20 also inhibits the effector phase of interactions involved in T-cell-dependent-B cell differentiation response. For these studies, CD4+ T cells were first activated with antigen or pokeweed mitogen, cultured with soluble HIV gp120 or medium for 2 hr, and washed. Coculture of gp120-treated preactivated T cells with autologous B cells resulted in impairment of IgG secretion, but did not affect IgM secretion significantly. The IgG secretion was restored by the addition of PMA (activator of protein kinase C) or forskolin (activator of adenylate cyclase), but not by the addition of ionomycin (inducer of intracellular calcium) to the T plus B cell cultures. A similar pattern of Ig secretion (IgM, no IgG) was observed with B cells of a patient with bare lymphocyte syndrome, indicating a requirement for MHC class II molecule interaction with T cells. These studies suggest that the effector phase of T-B cell interactions are impaired by gp120, and that the mechanism involves a signal transducing event(s), which is dependent upon cyclic AMP and/or protein kinase C. Furthermore, these latter reactions occur subsequent to T-B cell contact-dependent interactions at the effector phase, which involve MHC class II molecules on B cells and CD4 molecules on T cells.

Original languageEnglish (US)
Pages (from-to)169-182
Number of pages14
JournalCellular Immunology
Volume155
Issue number1
DOIs
StatePublished - Apr 15 1994

ASJC Scopus subject areas

  • Immunology

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