Analysis of B-lymphocyte differentiation in patients infected with hepatitis C virus.
To clarify whether some of the functions of B lymphocytes could be affected during hepatitis C virus (HCV) infection, phenotypic characteristics of B lymphocytes from HCV-infected patients and their capacity to differentiate into immunoglobulins (Ig)-secreting cells were studied. B lymphocytes differentiation was investigated for patients untreated and non-responders (n=9), treated and non-responders (n=6), responders (n=6), long-term responders (n=9) to therapy and seronegative controls (n=14) following in vitro stimulation with S. aureus strain Cowan I mitogen. HCV sequences in purified B lymphocytes were detected by RT-PCR. It was found that HCV-patients harbor a similar mean percentage of B cells and a normal level of naïve B cells (% IgM+/IgD+ cells=79.7 +/- 15.4 for untreated non-responders, 57.1 +/- 22.9 for treated non-responders, 44.3 +/- 29.1 for responders, 75.7 +/- 16 for long-term responders) as compared with controls. It was also found that peripheral blood mononuclear cells (PBMCs) of patients or controls produced similar amounts of IgG, A, and M in vitro. A total of 57% of untreated non-responders versus 17% of treated non-responders were able to produce HCV-specific antibodies. Interestingly, B lymphocytes from PBMCs able to secrete anti-HCV antibodies contained HCV positive strand RNA, although no systematic detection of the negative strand was found. These data suggest that signaling through the B cell receptor (BCR) in B lymphocytes of HCV-infected patients appears normal whatever their response to therapy. The capacity to secrete HCV-specific IgG seemed to be linked to the presence of positive strand RNA rather than virus replication.
Unité mixte CNRS/bioMérieux 2142, Lyon Cédex, France. Anne.Fournillier@ens-lyon.fr
Anne
A
Fournillier
Delphine
D
Freida
Thierry
T
Defrance
Philippe
P
Merle
Christian
C
Trépo
Geneviève
G
Inchauspé
D000328:Adult; D000368:Aged; D000921:Antibody-Producing Cells / Q000276:immunology; D018951:Antigens, CD20 / Q000032:analysis; D001402:B-Lymphocytes / Q000276:immunology*; D002452:Cell Count; D002454:Cell Differentiation; D005260:Female; D016174:Hepacivirus / Q000302:isolation & purification; D006526:Hepatitis C / Q000276:immunology* / Q000821:virology; D018937:Hepatitis C Antibodies / Q000378:metabolism; D019698:Hepatitis C, Chronic / Q000276:immunology* / Q000821:virology; D006801:Humans; D007136:Immunoglobulins / Q000378:metabolism; D007156:Immunologic Memory; D008103:Liver Cirrhosis / Q000276:immunology* / Q000821:virology; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D018951:Antigens, CD20; D018937:Hepatitis C Antibodies; D007136:Immunoglobulins; D011947:Receptors, Antigen, B-Cell