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 VH3(+) B cells, we probed the temporal development of VH3(+) antibodies in HIV-1-infected subjects over a 7-year period. We found that VH3(+) antibodies specific for the gp120 superantigen binding site are deficient. Since VH3(+) antibodies impart protective responses to infectious agents, we quantified VH3(+) antibodies in serum samples from HIV-seropositive slow progressors and from patients who progressed to AIDS-related manifestations. We found that paucity in VH3(+) antibodies is a marker of rapid clinical decline. Remarkably, anti-gp160 VH3(+) 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 VH3(+) antibodies play an important role in protection, and that their underexpression may accelerate disease progression. We propose that vaccine preparations able to trigger VH3(+) 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.
Juompan
L
L
Département d'Immunologie, Institut Pasteur, 75015 Paris, France.
Lambin
P
P
Zouali
M
M
D001666:Binding Sites, Antibody; D005260:Female; D015483:HIV Antibodies / Q000096:biosynthesis / Q000276:immunology*; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015658:HIV Infections / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology* / Q000302:isolation & purification; D006801:Humans; D008297:Male; D018089:Superantigens / Q000276:immunology; D019562:Viral Load
D015483:HIV Antibodies; D015699:HIV Envelope Protein gp120; D018089:Superantigens