title: Peripheral CD27-CD21- B-cells represent an exhausted lymphocyte population in hepatitis C cirrhosis.
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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Pennsylvania, USA.
authors.forename: Hiroyoshi
authors.initials: H
authors.lastname: Doi
authors.affiliation: Division of Gastroenterology, Department of Medicine, University of Pennsylvania, USA.
authors.forename: Shiroh
authors.initials: S
authors.lastname: Tanoue
authors.affiliation: 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.
authors.forename: David E
authors.initials: DE
authors.lastname: Kaplan
mesh_terms: D000328:Adult; D000368:Aged; D000917:Antibody Formation / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism; D005260:Female; D006526:Hepatitis C / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D016130:Immunophenotyping; D008103:Liver Cirrhosis / Q000150:complications / Q000276:immunology* / Q000378:metabolism; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D017464:Receptors, Complement 3d / Q000378:metabolism; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism; D055815:Young Adult
chemical_list: D011947:Receptors, Antigen, B-Cell; D017464:Receptors, Complement 3d; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7
keywords: Anergy; B-cell; CD21; Hepatitis C; Human; Lymphocyte