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

doi:10.1038/ni.2746

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

School of Medicine

Research output: Contribution to journal › Article › peer-review

68 Scopus citations

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 language	English (US)
Pages (from-to)	1256-1265
Number of pages	10
Journal	Nature Immunology
Volume	14
Issue number	12
DOIs	https://doi.org/10.1038/ni.2746
State	Published - Dec 2013

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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Jelicic, K., Cimbro, R., Nawaz, F., Huang, D. W., Zheng, X., Yang, J., Lempicki, R. A., Pascuccio, M., Van Ryk, D., Schwing, C., Hiatt, J., Okwara, N., Wei, D., Roby, G., David, A., Hwang, I. Y., Kehrl, J. H., Arthos, J., Cicala, C., & Fauci, A. S. (2013). The HIV-1 envelope protein gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression. Nature Immunology, 14(12), 1256-1265. https://doi.org/10.1038/ni.2746

Jelicic, K, Cimbro, R, Nawaz, F, Huang, DW, Zheng, X, Yang, J, Lempicki, RA, Pascuccio, M, Van Ryk, D, Schwing, C, Hiatt, J, Okwara, N, Wei, D, Roby, G, David, A, Hwang, IY, Kehrl, JH, Arthos, J, Cicala, C & Fauci, AS 2013, 'The HIV-1 envelope protein gp120 impairs B cell proliferation by inducing TGF-β1 production and FcRL4 expression', Nature Immunology, vol. 14, no. 12, pp. 1256-1265. https://doi.org/10.1038/ni.2746

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

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.",

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

note = "Funding Information: We thank C. Derdeyn for HIV sequence information; A. Introini for suggestions; and J. Weddle and A. Weddle for assistance with figure preparation. Supported by the Intramural Research Program of the US National Institutes of Health (National Institute of Allergy and Infectious Diseases).",

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doi = "10.1038/ni.2746",

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AU - Jelicic, Katija

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AU - Huang, Da Wei

AU - Zheng, Xin

AU - Yang, Jun

AU - Lempicki, Richard A.

AU - Pascuccio, Massimiliano

AU - Van Ryk, Donald

AU - Schwing, Catherine

AU - Hiatt, Joseph

AU - Okwara, Noreen

AU - Wei, Danlan

AU - Roby, Gregg

AU - David, Antonio

AU - Hwang, Ii Young

AU - Kehrl, John H.

AU - Arthos, James

AU - Cicala, Claudia

AU - Fauci, Anthony S.

N1 - Funding Information: We thank C. Derdeyn for HIV sequence information; A. Introini for suggestions; and J. Weddle and A. Weddle for assistance with figure preparation. Supported by the Intramural Research Program of the US National Institutes of Health (National Institute of Allergy and Infectious Diseases).

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

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