HIV-1 gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression

The humoral immune response following acute HIV-1 infection is delayed and ineffective. The HIV-1 envelope protein gp120 binds to and signals through α(4)β(7) on T cells. We show that gp120 also binds and signals through α(4)β(7) on naïve B cells, resulting in an abortive proliferative response. In primary B cells gp120 signaling through α(4)β(7) resulted in increased expression of the immunosuppressive cytokine TGF-β1 and the B cell inhibitory receptor FcRL4. Co-culture of B cells with HIV-1-infected autologous CD4(+) T cells also increased B cell FcRL4 expression. These findings indicate that, in addition to mediating chronic immune activation, viral proteins can contribute directly to HIV-1-associated B cell dysfunction. Our studies provide a mechanism whereby the virus may subvert the early HIV-1-specific humoral immune response.