Molecular analysis of V(H)I+ B lymphocytes in hepatitis C patients.
OBJECTIVE
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.


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.
Galli-Stampino
L
L
Department of Immunology, IRIS, Chiron S.r.l., Via Fiorentina, 1, 1-53100 Siena, Italy.
Pasqualini
A
A
Pozzato
G
G
Bonino
F
F
Filipponi
F
F
Mosca
M
M
Masciopinto
F
F
Abrignani
S
S
Uematsu
Y
Y
D001402:B-Lymphocytes / Q000276:immunology / Q000821:virology*; D016022:Case-Control Studies; D002999:Clone Cells / Q000276:immunology; D017931:DNA Primers; D005260:Female; D019698:Hepatitis C, Chronic / Q000235:genetics* / Q000276:immunology*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017423:Sequence Analysis, RNA
D017931:DNA Primers; D007143:Immunoglobulin Heavy Chains