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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Antibody Formation / immunology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Female
  • Hepatitis C / complications
  • Hepatitis C / immunology*
  • Hepatitis C / metabolism
  • Humans
  • Immunophenotyping
  • Liver Cirrhosis / complications
  • Liver Cirrhosis / immunology*
  • Liver Cirrhosis / metabolism
  • Lymphocyte Activation / immunology
  • Male
  • Middle Aged
  • Phenotype
  • Receptors, Antigen, B-Cell / metabolism
  • Receptors, Complement 3d / metabolism
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / metabolism
  • Young Adult


  • Receptors, Antigen, B-Cell
  • Receptors, Complement 3d
  • Tumor Necrosis Factor Receptor Superfamily, Member 7