The HIV-1 Envelope Protein gp120 Impairs B Cell Proliferation by Inducing TGF-β1 Production and FcRL4 Expression

Nat Immunol. 2013 Dec;14(12):1256-65. doi: 10.1038/ni.2746. Epub 2013 Oct 27.

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.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • B-Lymphocytes / cytology
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD4-Positive T-Lymphocytes / cytology
  • CD4-Positive T-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / virology
  • CHO Cells
  • Cell Proliferation*
  • Cells, Cultured
  • Coculture Techniques
  • Cricetinae
  • Cricetulus
  • Flow Cytometry
  • HIV Envelope Protein gp120 / genetics
  • HIV Envelope Protein gp120 / immunology*
  • HIV Envelope Protein gp120 / metabolism
  • HIV-1 / genetics
  • HIV-1 / immunology
  • HIV-1 / physiology
  • Host-Pathogen Interactions / immunology
  • Humans
  • Integrins / genetics
  • Integrins / immunology
  • Integrins / metabolism
  • Oligonucleotide Array Sequence Analysis
  • Protein Binding / immunology
  • Receptors, Fc / genetics
  • Receptors, Fc / immunology*
  • Receptors, Fc / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / immunology
  • Transcriptome / genetics
  • Transcriptome / immunology
  • Transforming Growth Factor beta1 / genetics
  • Transforming Growth Factor beta1 / immunology*
  • Transforming Growth Factor beta1 / metabolism

Substances

  • FCRL4 protein, human
  • HIV Envelope Protein gp120
  • Integrins
  • Receptors, Fc
  • Transforming Growth Factor beta1
  • gp120 protein, Human immunodeficiency virus 1
  • integrin alpha4beta7

Associated data

  • GEO/GSE49019