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

Katija Jelicic, Raffaello Cimbro, Fatima Nawaz, Da Wei Huang, Xin Zheng, Jun Yang, Richard A. Lempicki, Massimiliano Pascuccio, Donald Van Ryk, Catherine Schwing, Joseph Hiatt, Noreen Okwara, Danlan Wei, Gregg Roby, Antonio David, Ii Young Hwang, John H. Kehrl, James Arthos, Claudia Cicala, Anthony S. Fauci

Research output: Contribution to journalArticlepeer-review

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 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.

Original languageEnglish (US)
Pages (from-to)1256-1265
Number of pages10
JournalNature Immunology
Volume14
Issue number12
DOIs
StatePublished - Dec 2013

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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