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

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

PROVIDER: GSE49019 | GEO | 2013/10/17

SECONDARY ACCESSION(S): PRJNA212697

REPOSITORIES: GEO

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

Project description: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.

2013-10-17 | E-GEOD-49019 | biostudies-arrayexpress

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