Accumulation of B lymphocytes with a naive, resting phenotype in a subset of hepatitis C patients

J Immunol. 2003 Mar 15;170(6):3429-39. doi: 10.4049/jimmunol.170.6.3429.


Chronic infection with hepatitis C virus (HCV) is associated with disturbances of B lymphocyte activation and function: autoantibody production, mixed cryoglobulinemia, and B cell lymphomas. It has been proposed that these abnormalities reflect chronic antigenic stimulation or aberrant signaling through the B cell coreceptor, the latter mediated by binding of the HCV E2 glycoprotein to CD81. To test this hypothesis, we measured expression of activation and differentiation markers on peripheral blood B cells from patients with chronic HCV infection. Thirty-six HCV patients with and without mixed cryoglobulinemia were compared with 18 healthy control volunteers and 17 sustained virologic responders who had cleared HCV infection. Ten of the 36 HCV patient samples showed increased B cell frequencies; B cell frequency was higher in patients with more severe hepatic fibrosis. However, these samples lacked evidence of Ag-driven activation or proliferation. The expanded cells were low in the activation markers CD25, CD69, CD71, CD80, and CD86. Proliferation of circulating B cells was unchanged in HCV patients. These cells did not express the differentiation marker CD27, suggesting that they were not enriched in memory B cells. Furthermore, the expanded B cells expressed both IgD and IgM, suggesting that they were antigenically naive. Together, these results indicate that B cell expansion in the peripheral blood of HCV patients is not associated with Ag-mediated activation and differentiation. Instead, factors other than antigenic stimulation may promote the accumulation of peripheral blood B cells with a naive phenotype in a subset of HCV patients.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD / metabolism
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism*
  • B-Lymphocyte Subsets / pathology
  • CD5 Antigens / biosynthesis
  • Cell Division / immunology
  • Female
  • Flow Cytometry / statistics & numerical data
  • Hepatitis C / immunology*
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Humans
  • Immunophenotyping*
  • Interphase / immunology*
  • Ligands
  • Lymphocyte Activation
  • Lymphocyte Count / statistics & numerical data
  • Male
  • Membrane Proteins / metabolism
  • Middle Aged
  • Severity of Illness Index
  • Tetraspanin 28
  • Tumor Necrosis Factor Receptor Superfamily, Member 7 / biosynthesis
  • Viral Envelope Proteins / metabolism


  • Antigens, CD
  • CD5 Antigens
  • CD81 protein, human
  • Ligands
  • Membrane Proteins
  • Tetraspanin 28
  • Tumor Necrosis Factor Receptor Superfamily, Member 7
  • Viral Envelope Proteins
  • glycoprotein E2, Hepatitis C virus