BACKGROUND & AIMS: Chronic microbial infections are frequently associated with B-cell activation and polyclonal proliferation, potentially leading to autoimmunity and lymphoproliferative disorders. We assessed B-cell phenotype and function in chronic hepatitis B (HBV) and chronic hepatitis C (HCV) virus infection. METHODS: We studied 70 patients with chronic HCV infection, 34 with chronic HBV infection and 54 healthy controls. B-cell phenotype was assessed by flow cytometry using monoclonal antibodies specific for CD27, the CD69, CD71, and CD86 activation markers and the chemokine receptor CXCR3. Differentiation into immunoglobulin-producing cells (IPC) was analysed by ELISpot upon stimulation and with CD40 ligand±IL-10 as surrogate bystander T-cell help or CpG oligodeoxynucleotide±IL-2, as innate immunity signal. Proliferation was examined by flow cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) after stimulation with CpG. RESULTS: A significantly higher proportion of B cells from both HCV- and HBV-infected patients expressed activation markers compared with controls and a positive correlation was found between CXCR3(+) B cells and HCV RNA values. Memory B cells from patients with chronic HCV and HBV infections showed enhanced differentiation into IPC compared with controls, although this was restricted to IgG and at a lower level in HCV-compared with HBV-infected patients. Moreover, patients' activated B cells displayed significantly lower proliferative ability compared to healthy donors despite low expression of the FcRL4 exhaustion marker. CONCLUSIONS: B-cell activation, but not exhaustion, is common in chronic viral hepatitis. However, enhanced B-cell differentiation and deficient proliferative capacity were not associated with commitment to terminal differentiation.
BACKGROUND & AIMS:Chronic microbial infections are frequently associated with B-cell activation and polyclonal proliferation, potentially leading to autoimmunity and lymphoproliferative disorders. We assessed B-cell phenotype and function in chronic hepatitis B (HBV) and chronic hepatitis C (HCV) virus infection. METHODS: We studied 70 patients with chronic HCV infection, 34 with chronic HBV infection and 54 healthy controls. B-cell phenotype was assessed by flow cytometry using monoclonal antibodies specific for CD27, the CD69, CD71, and CD86 activation markers and the chemokine receptor CXCR3. Differentiation into immunoglobulin-producing cells (IPC) was analysed by ELISpot upon stimulation and with CD40 ligand±IL-10 as surrogate bystander T-cell help or CpG oligodeoxynucleotide±IL-2, as innate immunity signal. Proliferation was examined by flow cytometry using carboxyfluorescein diacetate succinimidyl ester (CFSE) after stimulation with CpG. RESULTS: A significantly higher proportion of B cells from both HCV- and HBV-infectedpatients expressed activation markers compared with controls and a positive correlation was found between CXCR3(+) B cells and HCV RNA values. Memory B cells from patients with chronic HCV and HBV infections showed enhanced differentiation into IPC compared with controls, although this was restricted to IgG and at a lower level in HCV-compared with HBV-infectedpatients. Moreover, patients' activated B cells displayed significantly lower proliferative ability compared to healthy donors despite low expression of the FcRL4 exhaustion marker. CONCLUSIONS: B-cell activation, but not exhaustion, is common in chronic viral hepatitis. However, enhanced B-cell differentiation and deficient proliferative capacity were not associated with commitment to terminal differentiation.
Authors: Hiroyoshi Doi; Tara K Iyer; Erica Carpenter; Hong Li; Kyong-Mi Chang; Robert H Vonderheide; David E Kaplan Journal: Hepatology Date: 2012-01-19 Impact factor: 17.425
Authors: Kevin B Walsh; John R Teijaro; Elina I Zuniga; Megan J Welch; Daniel M Fremgen; Shawn D Blackburn; Karl F von Tiehl; E John Wherry; Richard A Flavell; Michael B A Oldstone Journal: Cell Host Microbe Date: 2012-06-14 Impact factor: 21.023