Selective deficit in antibodies specific for the superantigen binding site of gp120 in HIV infection

HIV infection is characterized by accelerated apoptosis and progressive loss of B cells. To see whether these abnormalities are related to the property of gp120 to act as a superantigen for V-H(3+) B cells, we probed the temporal development of V-H(3+) antibodies in HTV-1-infected subjects over a 7-year period. We found that VH3+ antibodies specific for the gp120 superantigen binding site are deficient, Since V-H(3+) antibodies impart protective responses to infectious agents, we quantified V-H(3+) antibodies in serum samples from HIV-seropositive slow progressors and from patients who progressed to AIDS-related manifestations, We found that paucity in V-H(3+) antibodies is a marker of rapid clinical decline. Remarkably, anti-gp160 V-H(3+) antibodies showed a gradual decrease in progressors and, with time, varied depending on the viral load. We conclude that disease aggravation is associated with a decrease of the magnitude of the humoral response, that V-H(3+) antibodies play an important role in protection, and that their underexpression may accelerate disease progression. We propose that vaccine preparations able to trigger V-H(3+) antibodies might confer a better protection against HIV infection, This work also represents a novel mechanism of humoral deficiency resulting from the capacity of a viral antigen to affect an important subset of the B cell repertoire and to induce B cell death by apoptosis.