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

T-cell-dependent B cell differentiation involves two phases: an induct ive phase of T cell activation followed by an effector phase, which in volves 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, gp 120, at the inductive phase of T-cell-dependent B cell response. In this st udy we have investigated whether gp120 also inhibits the effector phas e 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 gpl20-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 rest ored by the addition of PMA (activator of protein kinase C) or forskol in (activator of adenylate cyclase), but not by the addition of ionomy cin (inducer of intracellular calcium) to the T plus B cell cultures. A similar pattern of Ig secretion (IgM, no IgG) was observed with B ce lls of a patient with bare lymphocyte syndrome, indicating a requireme nt for MHC class II molecule interaction with T cells. These studies s uggest that the effector phase of T-B cell interactions are impaired b y gp120, and that the mechanism involves a signal transducing event(s) , which is dependent upon cyclic AMP and/or protein kinase C. Furtherm ore, these latter reactions occur subsequent to T-B cell contact-depen dent interactions at the effector phase, which involve MHC class II mo lecules on B cells and CD4 molecules on T cells, (C) 1994 Academic Pre ss, Inc.