HIV-1 gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression via an α4β7-dependent mechanism

The anti-HIV humoral immune response following acute infection is delayed and ineffective. HIV envelope protein gp120 binds to and signals through α4β7 on T cells. We show that gp120 also binds and signals through α4β7 on B cells, resulting in an abortive proliferative response. In primary B cells, gp120 signaling through α4β7 resulted in increased expression of TGF-β1 and the B cell inhibitory receptor FcRL4. Co-culture of B cells with HIV-infected autologous CD4+ T cells also resulted in increased B cell FcRL4 expression. These findings indicate that, in addition to inducing chronic immune activation, viral proteins can contribute directly to HIV-associated B cell dysfunction, thus providing a mechanism whereby the virus subverts the early HIV-specific humoral immune response. Forty-two samples in two batches were run with different treatments and different time points.