Human immunodeficiency virus type-1 induces a regulatory B cell-like phenotype in vitro

Individuals infected with human immunodeficiency virus type-1(HIV-1)usually show a general dysregulation and hyper-activation of the immune system.A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described.However,the consequences of B-cell dysregulation are still poorly understood.We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli.The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+and CD8+T cells.We demonstrated that HIV-1 induces a phenotypic change in B cells towards a regulatory B-cell phenotype,showing a higher level of IL-10,TGF-β1,EBI3 or IL-12(p35)mRNA expression and acquiring an immunosuppressive profile.The acquisition of a Breg phenotype was confirmed by co-culture experiments where HIVtreated B cells reduced the proliferation and the TNFαproduction of CD4+or CD8+T cells.This suppressive ability of HIV-treated B cells was dependent on cell-to-cell contact between these B cells and effector cells.To our knowledge,these data provide the first evidence that HIV-1 can directly induce a regulatory B cell-like immunosuppressive phenotype,which could have the ability to impair specific immune responses.This dysregulation could constitute one of the mechanisms underlying unsuccessful efforts to develop an efficient vaccine against HIV-1.