Premium
Hepatitis C viraemia reversibly maintains subset of antigen‐specific T‐bet+ tissue‐like memory B cells
Author(s) -
Chang L.Y.,
Li Y.,
Kaplan D. E.
Publication year - 2017
Publication title -
journal of viral hepatitis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.329
H-Index - 100
eISSN - 1365-2893
pISSN - 1352-0504
DOI - 10.1111/jvh.12659
Subject(s) - virology , antigen , hepatitis b , biology , immunology , microbiology and biotechnology , chemistry
Summary Background: Chronic antigen exposure and/or ageing increases the frequency of T ‐ b ox e xpressed in T cells (T‐bet)‐expressing B‐lymphocytes in mice. The frequency and significance of B‐cell T‐bet expression during chronic hepatitis C ( HCV ) infection in human subjects has never been described. Methods: Healthy controls, cirrhotic and noncirrhotic HCV ‐infected patients, and non‐ HCV patients with cirrhosis were recruited. Peripheral blood mononuclear cells were phenotyped for expression of T‐bet and related markers by flow cytometry. In a subset of patients who underwent antiviral therapy and were cured of HCV infection (sustained virological response), the dynamics of T‐bet expression in B cells was monitored. After cure, convalescent B cells were tested for T‐bet expression after re‐exposure to infected plasma or recombinant HCV proteins. Results: Forty‐nine patients including 11 healthy donors, 30 hepatitis C‐infected individuals (nine with liver cancer, 13 with cirrhosis, eight without cirrhosis) and eight patients with cirrhosis due to non‐ HCV ‐related cause were recruited. We found that B cells in patients with chronic HCV exhibited increased frequency of T‐bet+ B cells relative to noninfected individuals (median 11.5% v. 2.2%, P <.0001) but that there were no significant differences between noncirrhotic, cirrhotic and cancer‐bearing infected individuals. T‐Bet + B cells expressed higher levels of CD 95, CXCR 3, CD 11c, CD 267 and Fc RL 5 compared to T‐bet − B cells and predominantly exhibit a tissue‐like memory CD 27 − CD 21 − phenotype independent of HCV infection. T‐bet + B cells in HCV ‐infected patients were more frequently class‐switched IgD − IgG + (40.4% vs. 26.4%, P =.012). Resolution of HCV infection with direct‐acting antiviral ( DAA ) therapy leads to a marked reduction in the frequency of T‐bet + B cells (median 14.1% pretreatment v. 6.7% end of treatment v. 6.1% SVR 12, P ≤.01). Re‐exposure of convalescent (cured) B cells to viremic plasma and recombinant HCV E2 protein led to re‐expression of T‐bet. Conclusion: Chronic antigenemia in chronic HCV infection induces and maintains an antigen‐specific T‐bet + B cell. These B cells share markers with tissue‐like memory B cells. Antigen‐driven T‐bet expression may be a critical suppressor of B‐cell activation in chronic HCV infection.