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 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 gp120 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.
Chirmule
N
N
Department of Pediatrics, North Shore University Hospital, Cornell University Medical College, Manhasset, New York 11030.
Wang
X P
XP
Hu
R
R
Oyaizu
N
N
Roifman
C
C
Pahwa
R
R
Kalyanaraman
V S
VS
Pahwa
S
S
D017951:Antigen Presentation; D001402:B-Lymphocytes / Q000276:immunology*; D015704:CD4 Antigens / Q000276:immunology; D002450:Cell Communication; D002454:Cell Differentiation / Q000187:drug effects*; D016207:Cytokines / Q000494:pharmacology; D005260:Female; D015699:HIV Envelope Protein gp120 / Q000494:pharmacology*; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D006801:Humans; D007074:Immunoglobulin G / Q000096:biosynthesis; D007075:Immunoglobulin M / Q000096:biosynthesis; D007223:Infant; D008214:Lymphocytes / Q000473:pathology; D015398:Signal Transduction; D013601:T-Lymphocytes / Q000187:drug effects* / Q000276:immunology*; D006377:T-Lymphocytes, Helper-Inducer / Q000187:drug effects / Q000276:immunology
D015704:CD4 Antigens; D016207:Cytokines; D015699:HIV Envelope Protein gp120; D000949:Histocompatibility Antigens Class II; D007074:Immunoglobulin G; D007075:Immunoglobulin M