The humoral immune response after acute infection with HIV-1 is delayed and ineffective. The HIV-1 envelope protein gp120 binds to and signals through integrin α 4 β 7 on T cells. We found that gp120 also bound to and signaled through α 4 β 7 on naive B cells, which resulted in an abortive proliferative response. In primary B cells, signaling by gp120 through α 4 β 7 resulted in increased expression of the immunosuppressive cytokine TGF-β1 and FcRL4, an inhibitory receptor expressed on B cells. Coculture of B cells with HIV-1-infected autologous CD4 + T cells also increased the expression of FcRL4 by B cells. Our findings indicated that in addition to mediating chronic activation of the immune system, viral proteins contributed directly to HIV-1-associated B cell dysfunction. Our studies identify a mechanism whereby the virus may subvert the early HIV-1-specific humoral immune response.
ASJC Scopus subject areas
- Immunology and Allergy