Direct impact of inactivated HIV-1 virions on B lymphocyte subsets.
Although there is no convincing evidence that HIV infects primary B cells, marked changes in B cell responses have been described in HIV-1-infected subjects, including B cell repertoire perturbations, depression of B cell memory and paucity of CD5(+) B cells. As it is hard to assess the consequences of these in vitro and ex vivo observations in patients, the pathogenic mechanisms responsible for the B cell deficit are unclear, and direct and indirect effects of HIV-1 remain possible. To gain further insight into the impact of HIV-1 on the B cell compartment in vivo, we used XenoMouse mice, mice genetically engineered to express human antibodies with an absence of mouse antibody expression. In these transgenic animals, B cells expressing a virtually full human Ig repertoire develop, which allows investigation of the in vivo consequences of confronting B cells expressing human immunoglobulins with HIV-1. We found that soluble gp120 induced an inversion in the B-1a/B-1b cell ratios, without impacting B-2 cells or affecting substantially the T cell compartment. Virion treatment specifically and dramatically depressed B-1a cells, which represent the majority of B-1 cells in normal mice. The observed B cell changes were associated with a functional alteration of the humoral response to tetanus toxoid. Thus, the results reveal a capacity of HIV-1 to specifically impact a highly specialized B cell subpopulation. Because there is evidence that human IgM memory B cells are functionally equivalent to murine B-1a cells, our findings suggest that gp120 may have a direct deleting activity on B cell memory.
Viau
Muriel
M
Inserm U430, Paris, France.
Veas
Francisco
F
Zouali
Moncef
M
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D018956:CD5 Antigens / Q000276:immunology; D017637:Clonal Deletion / Q000276:immunology; D015699:HIV Envelope Protein gp120 / Q000276:immunology*; D015497:HIV-1 / Q000276:immunology*; D006801:Humans; D007075:Immunoglobulin M / Q000276:immunology; D007156:Immunologic Memory / Q000276:immunology*; D051379:Mice; D008822:Mice, Transgenic; D013601:T-Lymphocytes / Q000276:immunology; D014771:Virion / Q000276:immunology*; D038301:Virus Inactivation
D018956:CD5 Antigens; D015699:HIV Envelope Protein gp120; D007075:Immunoglobulin M