Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 53-60 |
| Number of pages | 8 |
| Journal | Journal of Hepatology |
| Volume | 55 |
| Issue number | 1 |
| DOIs | |
| Publication status | Published - Jul 2011 |
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Keywords
- Activation markers
- B cells
- ELISpot
- Flow cytometry
- HBV
- HCV
ASJC Scopus subject areas
- Hepatology
Cite this
Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections. / Oliviero, Barbara; Cerino, Antonella; Varchetta, Stefania; Paudice, Enrica; Pai, Somnath; Ludovisi, Serena; Zaramella, Marco; Michelone, Giuseppe; Pugnale, Paolo; Negro, Francesco; Barnaba, Vincenzo; Mondelli, Mario U.
In: Journal of Hepatology, Vol. 55, No. 1, 07.2011, p. 53-60.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Enhanced B-cell differentiation and reduced proliferative capacity in chronic hepatitis C and chronic hepatitis B virus infections
AU - Oliviero, Barbara
AU - Cerino, Antonella
AU - Varchetta, Stefania
AU - Paudice, Enrica
AU - Pai, Somnath
AU - Ludovisi, Serena
AU - Zaramella, Marco
AU - Michelone, Giuseppe
AU - Pugnale, Paolo
AU - Negro, Francesco
AU - Barnaba, Vincenzo
AU - Mondelli, Mario U.
PY - 2011/7
Y1 - 2011/7
N2 - 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.
AB - 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.
KW - Activation markers
KW - B cells
KW - ELISpot
KW - Flow cytometry
KW - HBV
KW - HCV
UR - http://www.scopus.com/inward/record.url?scp=79958822254&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=79958822254&partnerID=8YFLogxK
U2 - 10.1016/j.jhep.2010.10.016
DO - 10.1016/j.jhep.2010.10.016
M3 - Article
C2 - 21145853
AN - SCOPUS:79958822254
VL - 55
SP - 53
EP - 60
JO - Journal of Hepatology
JF - Journal of Hepatology
SN - 0168-8278
IS - 1
ER -