Bacteria‐instructed B cells cross‐prime naïve CD8+ T cells triggering effective cytotoxic responses

Author:

García‐Ferreras Raquel1ORCID,Osuna‐Pérez Jesús1,Ramírez‐Santiago Guillermo1,Méndez‐Pérez Almudena1ORCID,Acosta‐Moreno Andrés M1ORCID,Del Campo Lara12ORCID,Gómez‐Sánchez María J13,Iborra Marta4,Herrero‐Fernández Beatriz56ORCID,González‐Granado José M578ORCID,Sánchez‐Madrid Francisco5910,Carrasco Yolanda R11ORCID,Boya Patricia12,Martínez‐Martín Nuria4ORCID,Veiga Esteban1ORCID

Affiliation:

1. Department of Molecular & Cellular Biology Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB‐CSIC) Madrid Spain

2. Departamento de Biología Celular, Facultad de Odontología Universidad Complutense de Madrid Madrid Spain

3. Department of Immunology, School of Medicine Complutense University of Madrid, 12 de Octubre Health Research Institute (imas12) Madrid Spain

4. Centro de Biología Molecular Severo Ochoa (CSIC‐UAM) Madrid Spain

5. LamImSys Lab Instituto de Investigación Hospital 12 de Octubre (imas12) Madrid Spain

6. Departamento de Fisiología, Facultad de Medicina Universidad Autónoma de Madrid (UAM) Madrid Spain

7. CIBER de Enfermedades Cardiovasculares Instituto de Salud Carlos III Madrid Spain

8. Department of Immunology, Ophthalmology and ENT, School of Medicine Universidad Complutense de Madrid Madrid Spain

9. Centro Nacional de Investigaciones Cardiovasculares (CNIC) Madrid Spain

10. Hospital Universitario de la Princesa, Instituto Investigación Sanitaria Princesa (IIS‐IP) Universidad Autónoma de Madrid Madrid Spain

11. Department of Immunology & Oncology Centro Nacional de Biotecnología, Consejo Superior de Investigaciones Científicas (CNB‐CSIC) Madrid Spain

12. Department of Neuroscience University of Fribourg Fribourg Switzerland

Abstract

AbstractIn addition to triggering humoral responses, conventional B cells have been described in vitro to cross‐present exogenous antigens activating naïve CD8+ T cells. Nevertheless, the way B cells capture these exogenous antigens and the physiological roles of B cell‐mediated cross‐presentation remain poorly explored. Here, we show that B cells capture bacteria by trans‐phagocytosis from previously infected dendritic cells (DC) when they are in close contact. Bacterial encounter “instructs” the B cells to acquire antigen cross‐presentation abilities, in a process that involves autophagy. Bacteria‐instructed B cells, henceforth referred to as BacB cells, rapidly degrade phagocytosed bacteria, process bacterial antigens and cross‐prime naïve CD8+ T cells which differentiate into specific cytotoxic cells that efficiently control bacterial infections. Moreover, a proof‐of‐concept experiment shows that BacB cells that have captured bacteria expressing tumor antigens could be useful as novel cellular immunotherapies against cancer.

Funder

“la Caixa” Foundation

Ministerio de Ciencia e Innovación

Publisher

Springer Science and Business Media LLC

Subject

Genetics,Molecular Biology,Biochemistry

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