LOCALIZATION OF B-CELL STIMULATORY ACTIVITY OF HIV-1 TO THE CARBOXYL TERMINUS OF GP41

Patients with AIDS are known to have B-cell hyperactivity. We have previously demonstrated that an extract of HIV-1 could induce differentiation of peripheral blood B lymphocytes of healthy volunteers into immunoglobulin-secreting cells. In an attempt to delineate the B-cell stimulatory subregion in HIV-1, we have investigated the influences of native glycoproteins and recombinant proteins of the envelope. The complete envelope glycoprotein, gpl60 and a recombinant protein in the carboxyl terminal region of gp41 termed PE-8 were effective in inducing terminal differentiation of normal peripheral blood B lymphocytes and did so in a T-lymphocyte-dependent manner. The activity was not present in the native exterior envelope glycoprotein, gpl20 and several other recombinant proteins, viz PE-2 an PE-3, which are in the amino terminal region of gpl20 or in env-9, a protein in the junctional region of gpl20 and gp41. Polyclonal and monoclonal antibodies directed to diverse regions of the envelope abrogated the influence of gpl60. The PE-8-induced B-cell differentiation was abrogated by goat anti-gpl60 antibody but not by goat anti-gpl20 antibody or monoclonal antibody to the amino terminal of gp41. These studies suggest that a putative polyclonal B-cell stimulatory epitope of HIV-1 is located in the carboxyl end of the envelope glycoprotein. © 1990, Mary Ann Liebert, Inc. All rights reserved.