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  • department
  • center
  • program_project
  • nrc
  • whocc
  • project
  • software
  • tool
  • patent
  • Administrative Staff
  • Assistant Professor
  • Associate Professor
  • Clinical Research Assistant
  • Full Professor
  • Graduate Student
  • Lab assistant
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  • Pharmacist
  • PhD Student
  • Physician
  • Post-doc
  • Project Manager
  • Research Associate
  • Research Engineer
  • Retired scientist
  • Technician
  • Undergraduate Student
  • Veterinary
  • Visiting Scientist
  • Deputy Director of Center
  • Deputy Director of Department
  • Deputy Director of National Reference Center
  • Deputy Head of Facility
  • Director of Center
  • Director of Department
  • Director of Institute
  • Director of National Reference Center
  • Group Leader
  • Head of Facility
  • Head of Operations
  • Head of Structure
  • Honorary President of the Departement
  • Labex Coordinator
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Scientific Fields
Diseases
Organisms
Applications
Technique
Starting Date
07
Sep 2015
Status
Completed
Members
5
Structures
2

About

 

Hepatitis C virus (HCV) infection can contribute to the development of autoimmune disorders, but the mechanisms responsible for HCV-associated autoimmunity are not well understood. In collaboration with Pr David Saadoun (Hôpital La pitié Salpétrière, Inserm U959) funded by the ANRS, we investigated the cellular and molecular processes by which abnormally expanded atypical memory (AtM) B cells participate to HCV-associated autoimmunity. We found that TLR9 stimulation of AtM B cells from patients with HCV-associated cryoglobulinemia vasculitis (CV) induces: (i) the secretion of TNFα and IgMs with rheumatoid factor activity by AtM; (ii) an AtM-specific transcriptional signature centered on TNFα overexpression; (iii) the secretion of IFNγ and TNFα by effector T cells and stimulate their proliferation and conversely, reduction of regulatory T-cell proliferation when co-cultured with AtM. Moreover, we showed that AtM B-cell expansions display intraclonal diversity of mutated IgM with features of antigen-driven maturation. AtM antibodies did not react against ubiquitous autoantigens or HCV antigens but rather, possessed rheumatoid factor activity with unique targeted epitopes on the human IgG Fc region. Thus, our data strongly suggest a central role for AtM in defective tolerance of HCV-CV patients through TLR9 reactivation of anergic AtM and production of IgM antibodies with rheumatoid factor activity. This work was published in: Comarmond C, Lorin V, Marques C, Maciejewski-Duval A, Joher N, Planchais C, Touzot M, Biard L, Hieu T, Quiniou V, Desbois AC, Rosenzwajg M, Klatzmann D, Cacoub P, Mouquet H, Saadoun D. TLR9 Signaling in HCV-Associated Atypical Memory B Cells Triggers Th1 and Rheumatoid Factor Autoantibody Responses. J Hepatol. 2019 Jul 4. pii: S0168-8278(19)30401-5. doi: 10.1016/j.jhep.2019.06.029. [Epub ahead of print]

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