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

K Jelicic, R Cimbro, F Nawaz, DW Huang, X Zheng… - Nature …, 2013 - nature.com
K Jelicic, R Cimbro, F Nawaz, DW Huang, X Zheng, J Yang, RA Lempicki, M Pascuccio…
Nature immunology, 2013nature.com
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 α4β7 on T cells. We
found that gp120 also bound to and signaled through α4β7 on naive B cells, which resulted
in an abortive proliferative response. In primary B cells, signaling by gp120 through α4β7
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 …
Abstract
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 α4β7 on T cells. We found that gp120 also bound to and signaled through α4β7 on naive B cells, which resulted in an abortive proliferative response. In primary B cells, signaling by gp120 through α4β7 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.
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