Antibody production and in vitro behavior of CD27-defined B-cell subsets: persistent hepatitis C virus infection changes the rules.
There is growing interest in the tendency of B cells to change their functional program in response to overwhelming antigen loading, perhaps by regulating specific parameters, such as efficiency of activation, proliferation rate, differentiation to antibody-secreting cells (ASC), and rate of cell death in culture. We show that individuals persistently infected with hepatitis C virus (HCV) carry high levels of circulating immunoglobulin G (IgG) and IgG-secreting cells (IgG-ASC). Thus, generalized polyclonal activation of B-cell functions may be supposed. While IgGs include virus-related and unrelated antibodies, IgG-ASC do not include HCV-specific plasma cells. Despite signs of widespread activation, B cells do not accumulate and memory B cells seem to be reduced in the blood of HCV-infected individuals. This apparent discrepancy may reflect the unconventional activation kinetics and functional responsiveness of the CD27+ B-cell subset in vitro. Following stimulation with T-cell-derived signals in the absence of B-cell receptor (BCR) engagement, CD27+ B cells do not expand but rapidly differentiate to secrete Ig and then undergo apoptosis. We propose that their enhanced sensitivity to BCR-independent noncognate T-cell help maintains a constant level of nonspecific serum antibodies and ASC and serves as a backup mechanism of feedback inhibition to prevent exaggerated B-cell responses that could be the cause of significant immunopathology.
Department of Internal Medicine and Clinical Oncology, University of Bari Medical School, Policlinico-11, Piazza G. Cesare, 70124 Bari, Italy. v.racanelli@dimo.uniba.it
Vito
V
Racanelli
Maria Antonia
MA
Frassanito
Patrizia
P
Leone
Maria
M
Galiano
Valli
V
De Re
Franco
F
Silvestris
Franco
F
Dammacco
D000328:Adult; D000595:Amino Acid Sequence; D017209:Apoptosis; D016175:B-Lymphocyte Subsets / Q000276:immunology*; D005260:Female; D018937:Hepatitis C Antibodies / Q000097:blood*; D019698:Hepatitis C, Chronic / Q000276:immunology*; D006801:Humans; D008213:Lymphocyte Activation; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D013601:T-Lymphocytes / Q000502:physiology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000502:physiology*
D018937:Hepatitis C Antibodies; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7