Expansion of Functionally Anergic CD21 −/low Marginal Zone-like B Cell Clones in Hepatitis C Virus Infection-Related Autoimmunity - Sorbonne Université
Article Dans Une Revue Journal of Immunology Année : 2011

Expansion of Functionally Anergic CD21 −/low Marginal Zone-like B Cell Clones in Hepatitis C Virus Infection-Related Autoimmunity

Florence Joly
  • Fonction : Auteur
  • PersonId : 989351
Philippe Benech

Résumé

Homeostasis of peripheral B cell subsets is disturbed during chronic hepatitis C virus (HCV) infection, leading to the occurrence of autoimmunity and B cell lymphoproliferation. However, mechanisms by which HCV causes lymphoproliferation remain controversial. We report in this article on the elevated number of clonal CD21(-/low)IgM(+)CD27(+) marginal zone (MZ)-like B cells, which correlates with autoimmunity and lymphoproliferation in HCV patients. We found an increase in autoreactive BCRs using V(H)1-69 and V(H)4-34 genes in CD21(-/low) MZ B cells. CD21(-/low) MZ B cells showed impaired calcium-mediated signaling, did not upregulate activation markers, and did not proliferate in response to BCR triggering. CD21(-/low) MZ B cells also were prone to dying faster than their CD21(+) counterparts, suggesting that these B cells were anergic. CD21(-/low) MZ B cells, in contrast, remained responsive to TLR9 stimulation. Gene array analyses revealed the critical role of Early growth response 2 and Cbl-b in the induction of anergy. Therefore, HCV patients who display high frequencies of unresponsive CD21(-/low) MZ B cells are more susceptible to developing autoimmunity and/or lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.

Dates et versions

hal-02565763 , version 1 (06-05-2020)

Identifiants

Citer

Benjamin Terrier, Florence Joly, Thomas Vazquez, Philippe Benech, Michelle Rosenzwajg, et al.. Expansion of Functionally Anergic CD21 −/low Marginal Zone-like B Cell Clones in Hepatitis C Virus Infection-Related Autoimmunity. Journal of Immunology, 2011, 187 (12), pp.6550-6563. ⟨10.4049/jimmunol.1102022⟩. ⟨hal-02565763⟩
65 Consultations
0 Téléchargements

Altmetric

Partager

More