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Published on: April 17, 2017
Molecular analysis of V(H)I+ B lymphocytes in hepatitis C patients
L Galli-Stampino1, A Pasqualini, G Pozzato
1Department of Immunology, IRIS, Chiron S.r.l., Via Fiorentina, 1, 1-53100 Siena, Italy.
Insights
Hepatitis C virus infection can lead to clonal B-cell expansion, even in patients without lymphoproliferative disorders. This expansion shows broad immunoglobulin gene usage, suggesting a potential precursor stage for conditions like non-Hodgkin lymphoma.
Area of Science:
- Immunology
- Virology
- Hematology
Background:
- Hepatitis C virus (HCV) infection is linked to lymphoproliferative disorders, including essential mixed cryoglobulinemia and B-cell non-Hodgkin lymphoma.
- These disorders often exhibit preferential usage of VHI family immunoglobulin gene products.
- The study investigates whether clonal B-cell expansion occurs in HCV-infected patients without these overt lymphoproliferative conditions.
Purpose of the Study:
- To determine if clonal B-cell expansion occurs in hepatitis C virus-infected patients without essential mixed cryoglobulinemia or non-Hodgkin lymphoma.
- To analyze immunoglobulin heavy chain (VHI) gene usage in these patients.
- To explore the relationship between HCV infection, B-cell expansion, and the potential development of lymphoproliferative disorders.
Main Methods:
- Studied four hepatitis C virus-positive patients undergoing liver transplantation.
- Collected peripheral blood, intra-hepatic, and lymph node B cells.
- Utilized reverse transcription-polymerase chain reaction (RT-PCR) to analyze VHI family sequences, with controls including a hepatocellular carcinoma patient and healthy donors.
Main Results:
- Clonally expanded B lymphocytes, identified by immunoglobulin heavy chain sequences, were found in three of the four HCV-infected patients.
- These expanded B-cell populations demonstrated a wide range of immunoglobulin heavy chain gene usage.
- No significant findings were reported for the control groups.
Conclusions:
- Hepatitis C virus infection can induce significant B-cell expansion with considerable clonal variation.
- The observed clonal expansion may represent a non-malignant precursor state.
- Restricted V gene usage in established HCV-associated non-Hodgkin lymphoma suggests selection mechanisms may drive progression from these expanded B-cell populations to lymphoma.
Background And Aims:
Hepatitis C virus infection is often associated with lymphoproliferative disorders such as essential mixed cryoglobulinemia and B-cell non-Hodgkin lymphoma, which show preferential expression of VHI family products. By analyzing immunoglobulin heavy chain usage, we addressed the question of whether or not clonal B-cell expansion occurrs in patients free of essential mixed cryoglobulinemia or non-Hodgkin lymphoma.
Patients And Methods:
Four hepatitis C virus-positive patients, all undergoing liver transplantation, were studied. Peripheral blood, intra-hepatic, and lymph node lymphocytes were used as a source of B cells. A patient with hepatocellular carcinoma and fresh blood from four healthy donors were used as negative controls. VHI family sequences were cloned and analyzed by reverse transcription-polymerase chain reaction.
Results:
Immunoglobulin heavy chain sequences from clonally expanded B lymphocytes were identified in three out of four hepatitis C virus-infected patients. The clonally expanded B lymphocyte populations showed a broad spectra of immunoglobulin heavy chain gene usage.
Conclusions:
HCV infection can induce B-cell expansion with larger clonal variation. The restricted V gene usage in hepatitis C virus-associated non-Hodgkin lymphoma suggests that there may be selection mechanisms to develop non-Hodgkin lymphoma from non-malignant, clonally expanded B-cell populations in hepatitis C virus-infected patients.
