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Clin Immunol. 2014 Feb;150(2):184-91. doi: 10.1016/j.clim.2013.12.001. Epub 2013 Dec 17.

Peripheral CD27-CD21- B-cells represent an exhausted lymphocyte population in hepatitis C cirrhosis.

Author information

1
Division of Gastroenterology, Department of Medicine, University of Pennsylvania, USA.
2
Medicine and Research Services, Philadelphia VA Medical Center, Philadelphia, PA, USA; Division of Gastroenterology, Department of Medicine, University of Pennsylvania, USA. Electronic address: dakaplan@mail.med.upenn.edu.

Abstract

Hepatitis C cirrhosis is associated with a profound disappearance of memory B-cells. We sought to determine if this loss is associated with the expansion of the CD27(-)CD21(-) tissue-like memory B-cells with features of B-cell exhaustion. To this end, we quantified the frequency of CD27(-)CD21(-) B-cells in healthy, non-cirrhotic HCV-infected, and cirrhotic patients. We examined the expression of putative inhibitory receptors, the proliferative and immunoglobulin-secreting capacity of CD27/CD21-defined B-cell subsets upon B-cell receptor and/or CD40 stimulation. We found that CD27(-)CD21(-) B-cells are significantly increased in frequency relative to healthy donors in HCV-infected patients. CD27(-)CD21(-) B-cells were hypoproliferative relative to naïve and resting memory B-cells upon agonistic stimulation, but retained similar capacity for antibody secretion.

CONCLUSION:

CD27(-)CD21(-) tissue-like memory B-cells with exhausted proliferation circulate at increased frequency in cirrhotic and non-cirrhotic HCV-infected patients. This B-cell subset does not appear anergic, exhibiting immunoglobulin-secreting capacity on CD40 agonism indistinguishable from other CD27/CD21-defined B-cell subsets.

KEYWORDS:

Anergy; B-cell; CD21; Hepatitis C; Human; Lymphocyte

PMID:
24434272
PMCID:
PMC4580910
DOI:
10.1016/j.clim.2013.12.001
[Indexed for MEDLINE]
Free PMC Article
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