Clonal B cells in patients with hepatitis C virus-associated mixed cryoglobulinemia contain an expanded anergic CD21 low B-cell subset Academic Article uri icon


MeSH Major

  • B-Lymphocyte Subsets
  • Cryoglobulinemia
  • Hepatitis C, Chronic


  • Hepatitis C virus (HCV) is associated with the B-cell lymphoproliferative disorders mixed cryoglobulinemia (MC) and non-Hodgkin lymphoma. We have previously reported that HCV(+)MC(+) patients have clonal expansions of hypermutated, rheumatoid factor-bearing marginal zone-like IgM(+)CD27(+) peripheral B cells using the V(H)1-69 gene. Here we coupled transcriptional profiling with immunophenotypic and functional studies to ascertain these cells' role in MC pathogenesis. Despite their fundamental role in MC disease, these B cells have overall transcriptional features of anergy and apoptosis instead of neoplastic transformation. Highly up-regulated genes include SOX5, CD11C, galectin-1, and FGR, similar to a previously described FCRL4(+) memory B-cell subset and to an "exhausted," anergic CD21(low) memory B-cell subset in HIV(+) patients. Moreover, HCV(+)MC(+) patients' clonal peripheral B cells are enriched with CD21(low), CD11c(+), FCRL4(high), IL-4R(low) memory B cells. In contrast to the functional, rheumatoid factor-secreting CD27(+)CD21(high) subset, the CD27(+)CD21(low) subpopulation exhibits decreased calcium mobilization and does not efficiently differentiate into rheumatoid factor-secreting plasmablasts, suggesting that a large proportion of HCV(+)MC(+) patients' clonally expanded peripheral B cells is prone to anergy and/or apoptosis. Down-regulation of multiple activation pathways may represent a homeostatic mechanism attenuating otherwise uncontrolled stimulation of circulating HCV-containing immune complexes.

publication date

  • May 19, 2011



  • Academic Article



  • eng

PubMed Central ID

  • PMC3109715

Digital Object Identifier (DOI)

  • 10.1182/blood-2010-10-312942

PubMed ID

  • 21421840

Additional Document Info

start page

  • 5425

end page

  • 37


  • 117


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