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 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.
authors.affiliation: Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Katija
authors.initials: K
authors.lastname: Jelicic
authors.forename: Raffaello
authors.initials: R
authors.lastname: Cimbro
authors.forename: Fatima
authors.initials: F
authors.lastname: Nawaz
authors.forename: Da Wei
authors.initials: da W
authors.lastname: Huang
authors.forename: Xin
authors.initials: X
authors.lastname: Zheng
authors.forename: Jun
authors.initials: J
authors.lastname: Yang
authors.forename: Richard A
authors.initials: RA
authors.lastname: Lempicki
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Pascuccio
authors.forename: Donald
authors.initials: D
authors.lastname: Van Ryk
authors.forename: Catherine
authors.initials: C
authors.lastname: Schwing
authors.forename: Joseph
authors.initials: J
authors.lastname: Hiatt
authors.forename: Noreen
authors.initials: N
authors.lastname: Okwara
authors.forename: Danlan
authors.initials: D
authors.lastname: Wei
authors.forename: Gregg
authors.initials: G
authors.lastname: Roby
authors.forename: Antonio
authors.initials: A
authors.lastname: David
authors.forename: Ii Young
authors.initials: IY
authors.lastname: Hwang
authors.forename: John H
authors.initials: JH
authors.lastname: Kehrl
authors.forename: James
authors.initials: J
authors.lastname: Arthos
authors.forename: Claudia
authors.initials: C
authors.lastname: Cicala
authors.forename: Anthony S
authors.initials: AS
authors.lastname: Fauci
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D015496:CD4-Positive T-Lymphocytes / Q000166:cytology / Q000276:immunology / Q000821:virology; D016466:CHO Cells; D049109:Cell Proliferation; D002478:Cells, Cultured; D018920:Coculture Techniques; D006224:Cricetinae; D003412:Cricetulus; D005434:Flow Cytometry; D015699:HIV Envelope Protein gp120 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D015497:HIV-1 / Q000235:genetics / Q000276:immunology / Q000502:physiology; D054884:Host-Pathogen Interactions / Q000276:immunology; D006801:Humans; D016023:Integrins / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D020411:Oligonucleotide Array Sequence Analysis; D011485:Protein Binding / Q000276:immunology; D011961:Receptors, Fc / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D059467:Transcriptome / Q000235:genetics / Q000276:immunology; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000276:immunology* / Q000378:metabolism
chemical_list: C423544:FCRL4 protein, human; D015699:HIV Envelope Protein gp120; D016023:Integrins; D011961:Receptors, Fc; D053773:Transforming Growth Factor beta1; C514793:gp120 protein, Human immunodeficiency virus 1; C071777:integrin alpha4beta7