Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3923-3934 |
| Number of pages | 12 |
| Journal | Journal of Virology |
| Volume | 80 |
| Issue number | 8 |
| DOIs | |
| Publication status | Published - Apr 2006 |
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ASJC Scopus subject areas
- Immunology
Cite this
Antibody production and in vitro behavior of CD27-defined B-cell subsets : Persistent hepatitis C virus infection changes the rules. / Racanelli, Vito; Frassanito, Maria Antonia; Leone, Patrizia; Galiano, Maria; De Re, Valli; Silvestris, Franco; Dammacco, Franco.
In: Journal of Virology, Vol. 80, No. 8, 04.2006, p. 3923-3934.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Antibody production and in vitro behavior of CD27-defined B-cell subsets
T2 - Persistent hepatitis C virus infection changes the rules
AU - Racanelli, Vito
AU - Frassanito, Maria Antonia
AU - Leone, Patrizia
AU - Galiano, Maria
AU - De Re, Valli
AU - Silvestris, Franco
AU - Dammacco, Franco
PY - 2006/4
Y1 - 2006/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33645796706&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33645796706&partnerID=8YFLogxK
U2 - 10.1128/JVI.80.8.3923-3934.2006
DO - 10.1128/JVI.80.8.3923-3934.2006
M3 - Article
C2 - 16571809
AN - SCOPUS:33645796706
VL - 80
SP - 3923
EP - 3934
JO - Journal of Virology
JF - Journal of Virology
SN - 0022-538X
IS - 8
ER -