| Autor: |
Terrier B; Laboratoire I3 Immunologie, Immunopathologie, Immunothérapeutique, Centre National de la Recherche Scientifique Unité Mixte de Recherche 7211 et INSERM U959, Groupe Hospitalier Pitié-Salpétrière, Université Pierre et Marie Curie, F-75013 Paris, France., Joly F, Vazquez T, Benech P, Rosenzwajg M, Carpentier W, Garrido M, Ghillani-Dalbin P, Klatzmann D, Cacoub P, Saadoun D |
| Jazyk: |
angličtina |
| Zdroj: |
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2011 Dec 15; Vol. 187 (12), pp. 6550-63. Date of Electronic Publication: 2011 Nov 14. |
| DOI: |
10.4049/jimmunol.1102022 |
| Abstrakt: |
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. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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