Abstract
Chronic hepatitis C virus (HCV) infection is characterized by persistent B-cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B-cell subset distribution, we examined ex vivo frequencies and B-cell inhibitory receptor expression in 37 chronic HCV-infected patients and 25 healthy donors (HD). In addition, we determined whether short-term exposure to culture-derived HCV (HCVcc) resulted in B-cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue-like memory (TLM) B cells in HCV-infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor-like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B-cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell-free HCVcc in vitro did not result in B-cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV-infected patients but not in HD, in whom cell-associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B-cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B-cell subsets does not impair virus-induced B-cell activation.
| Original language | English |
|---|---|
| Pages (from-to) | 391-398 |
| Number of pages | 8 |
| Journal | Journal of Viral Hepatitis |
| Volume | 22 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - Apr 1 2015 |
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Keywords
- activation
- B cells
- FcRL4
- hepatitis C virus
ASJC Scopus subject areas
- Hepatology
- Infectious Diseases
- Virology
- Medicine(all)
Cite this
Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus-induced activation. / Oliviero, B.; Mantovani, S.; Ludovisi, S.; Varchetta, S.; Mele, D.; Paolucci, S.; Baldanti, F.; Mondelli, Mario U.
In: Journal of Viral Hepatitis, Vol. 22, No. 4, 01.04.2015, p. 391-398.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Skewed B cells in chronic hepatitis C virus infection maintain their ability to respond to virus-induced activation
AU - Oliviero, B.
AU - Mantovani, S.
AU - Ludovisi, S.
AU - Varchetta, S.
AU - Mele, D.
AU - Paolucci, S.
AU - Baldanti, F.
AU - Mondelli, Mario U.
PY - 2015/4/1
Y1 - 2015/4/1
N2 - Chronic hepatitis C virus (HCV) infection is characterized by persistent B-cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B-cell subset distribution, we examined ex vivo frequencies and B-cell inhibitory receptor expression in 37 chronic HCV-infected patients and 25 healthy donors (HD). In addition, we determined whether short-term exposure to culture-derived HCV (HCVcc) resulted in B-cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue-like memory (TLM) B cells in HCV-infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor-like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B-cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell-free HCVcc in vitro did not result in B-cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV-infected patients but not in HD, in whom cell-associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B-cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B-cell subsets does not impair virus-induced B-cell activation.
AB - Chronic hepatitis C virus (HCV) infection is characterized by persistent B-cell activation, with enhanced differentiation and reduced proliferative ability. To assess the possible role of HCV in altering B-cell subset distribution, we examined ex vivo frequencies and B-cell inhibitory receptor expression in 37 chronic HCV-infected patients and 25 healthy donors (HD). In addition, we determined whether short-term exposure to culture-derived HCV (HCVcc) resulted in B-cell subset skewing and/or activation. There was a statistically significant increase in the frequencies of immature transitional, activated memory and tissue-like memory (TLM) B cells in HCV-infected patients compared with HD. We also found that the frequency of memory B cells correlated with serum HCV RNA levels. The proportion of B cells expressing the marker of exhaustion Fc receptor-like 4 (FcRL4) was generally low even though significantly higher in the patients' memory B-cell compartment compared with HD, and a positive correlation was found between the frequencies of the patients' TLM FcRL4+ B cells and serum alanine aminotransferase and histological activity index at liver biopsy. Exposure to cell-free HCVcc in vitro did not result in B-cell skewing but induced significant activation of naïve, TLM and resting memory B cells in HCV-infected patients but not in HD, in whom cell-associated virus was an absolute requirement for activation of memory B cells. These findings provide corroborative evidence in favour of significant B-cell subset skewing in chronic HCV infection and in addition show that expression of exhaustion markers in selected B-cell subsets does not impair virus-induced B-cell activation.
KW - activation
KW - B cells
KW - FcRL4
KW - hepatitis C virus
UR - http://www.scopus.com/inward/record.url?scp=84925588616&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84925588616&partnerID=8YFLogxK
U2 - 10.1111/jvh.12336
DO - 10.1111/jvh.12336
M3 - Article
C2 - 25258145
AN - SCOPUS:84925588616
VL - 22
SP - 391
EP - 398
JO - Journal of Viral Hepatitis
JF - Journal of Viral Hepatitis
SN - 1352-0504
IS - 4
ER -