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Human immunodeficiency virus type-1 induces a regulatory B cell-like phenotype in vitro

Cellular & Molecular Immunology volume 15, pages 917–933 (2018)Cite this article

Abstract

Individuals infected with human immunodeficiency virus type-1 (HIV-1) usually show a general dysregulation and hyper-activation of the immune system. A direct influence of HIV-1 particles on B-cell phenotypes and functions has been previously described. However, the consequences of B-cell dysregulation are still poorly understood. We evaluated the phenotypic changes in primary B cells after direct contact with HIV-1 particles in comparison with different types of stimuli. The functionality of treated B cells was challenged in co-culture experiments with autologous CD4+ and CD8+ T cells. We demonstrated that HIV-1 induces a phenotypic change in B cells towards a regulatory B-cell phenotype, showing a higher level of IL-10, TGF-β1, EBI3 or IL-12(p35) mRNA expression and acquiring an immunosuppressive profile. The acquisition of a Breg phenotype was confirmed by co-culture experiments where HIV-treated B cells reduced the proliferation and the TNFα production of CD4+ or CD8+ T cells. This suppressive ability of HIV-treated B cells was dependent on cell-to-cell contact between these B cells and effector cells. To our knowledge, these data provide the first evidence that HIV-1 can directly induce a regulatory B cell-like immunosuppressive phenotype, which could have the ability to impair specific immune responses. This dysregulation could constitute one of the mechanisms underlying unsuccessful efforts to develop an efficient vaccine against HIV-1.

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Acknowledgements

We acknowledge the centers of transfusion of Madrid for providing the buffy coats. We acknowledge Dr Laura Díaz from the Cytometry unit of IiSGM for sample analysis and Dr Maribel Clemente from the Cell Culture unit of IiSGM. This work was partially supported by Ministry of Economy and Competitiveness ISCIII-FIS grants PI12/01763, PI12/00934 and PI15/00923, and co-financed by ERDF (FEDER) Funds from the European Commission, ‘A way of making Europe’. JL-A was supported by a Grant from IiSGM. AP-S was supported by the Youth Employment Program co-financed by the Madrid community and FEDER Founds. RC-R was supported by the ‘Miguel Servet’ program (CPII13/00033), and MP by the Spanish MICINN through the Ramón y Cajal (RYC-2009-05486). All work was performed in the Laboratorio de Inmuno-Biología Molecular, HGUGM (IiSGM) led by M-AM-F.

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Authors and Affiliations

  1. Laboratorio de Inmuno-Regulación, Immunology Department, Pabellón de Medicina y Cirugía Experimental, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), Calle Máiquez, 9, 28009, Madrid, Spain

    Jacobo Lopez-Abente, Adrián Prieto-Sanchez, Rafael Correa-Rocha & Marjorie Pion

  2. Laboratorio de Inmuno-Biología Molecular, Immunology Department, Hospital General Universitario Gregorio Marañón, Instituto de Investigación Sanitaria Gregorio Marañón (IiSGM), C/Dr. Esquerdo 46, 28007, Madrid, Spain

    Maria-Ángeles Muñoz-Fernandez & Marjorie Pion

  3. Networking Research Center on Bioengineering, Biomaterials and Nanomedicine (CIBER-BBN), C/ Monforte de Lemos 3-5, Pabellón 11, 28029, Madrid, Spain

    Maria-Ángeles Muñoz-Fernandez & Marjorie Pion

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  1. Jacobo Lopez-Abente
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Correspondence to Marjorie Pion.

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Lopez-Abente, J., Prieto-Sanchez, A., Muñoz-Fernandez, MÁ. et al. Human immunodeficiency virus type-1 induces a regulatory B cell-like phenotype in vitro . Cell Mol Immunol 15, 917–933 (2018). https://doi.org/10.1038/cmi.2017.48

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