Intrahepatic B cell clonal expansions and extrahepatic manifestations of chronic HCV infection

Domenico Sansonno, Gianfranco Lauletta, Valli De Re, Felicia Anna Tucci, Pietro Gatti, Vito Racanelli, Mauro Boiocchi, Franco Dammacco

Research output: Contribution to journalArticlepeer-review


B cell repertoire in three biological compartments (liver, bone marrow and peripheral blood) of 30 unselected patients chronically infected with HCV has been characterized. Restriction of humoral immune response defined by enrichment of B cell clonal expansions occurred in the liver of 15 patients (50%), in the bone marrow and peripheral blood of 2 (6.7%) and 8 (26.7%) patients, respectively. An in situ hybridization technique was developed for the detection of dominant B cell clones in patients with monoclonal expansions. It was shown that morphologically distinct B cell expansion contributes to the formation of intraportal follicle-like structures. Sequence analyses of CDRH3 gene segments revealed a wide range of variations. Clones derived from the same founder were demonstrated simultaneously in the three compartments explored. The occurrence of B cell clonal expansions profoundly influenced the clinical expression of HCV infection, since it was associated with extrahepatic manifestations. In sharp contrast, no extrahepatic signs or disease occurred in patients without evidence of intrahepatic B cell clonalities. These findings emphasize the profound B cell function derangement in at least half of HCV-infected patients. Thus, the restriction of V gene usage has a direct impact on the clinical spectrum of HCV infection.

Original languageEnglish
Pages (from-to)126-136
Number of pages11
JournalEuropean Journal of Immunology
Issue number1
Publication statusPublished - Jan 2004


  • B cell immune response
  • Cryoglobulinemia
  • Hepatitis C virus
  • Lymphoproliferation

ASJC Scopus subject areas

  • Immunology


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