Antibody production and in vitro behavior of CD27-defined B-cell subsets

Persistent hepatitis C virus infection changes the rules

Vito Racanelli, Maria Antonia Frassanito, Patrizia Leone, Maria Galiano, Valli De Re, Franco Silvestris, Franco Dammacco

Research output: Contribution to journalArticle

52 Citations (Scopus)

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 languageEnglish
Pages (from-to)3923-3934
Number of pages12
JournalJournal of Virology
Volume80
Issue number8
DOIs
Publication statusPublished - Apr 2006

Fingerprint

B-Lymphocyte Subsets
Hepatitis C virus
antibody formation
Virus Diseases
Hepacivirus
B-lymphocytes
Antibody Formation
B-Lymphocytes
Antibody-Producing Cells
infection
immunoglobulin G
antibodies
Immunoglobulin G
T-lymphocytes
T-Lymphocytes
cells
Gastrin-Secreting Cells
immunopathology
In Vitro Techniques
Antibodies

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 journalArticle

Racanelli, Vito ; Frassanito, Maria Antonia ; Leone, Patrizia ; Galiano, Maria ; De Re, Valli ; Silvestris, Franco ; Dammacco, Franco. / Antibody production and in vitro behavior of CD27-defined B-cell subsets : Persistent hepatitis C virus infection changes the rules. In: Journal of Virology. 2006 ; Vol. 80, No. 8. pp. 3923-3934.
@article{73f608dea905406199c90e9c644a1eb0,
title = "Antibody production and in vitro behavior of CD27-defined B-cell subsets: Persistent hepatitis C virus infection changes the rules",
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.",
author = "Vito Racanelli and Frassanito, {Maria Antonia} and Patrizia Leone and Maria Galiano and {De Re}, Valli and Franco Silvestris and Franco Dammacco",
year = "2006",
month = "4",
doi = "10.1128/JVI.80.8.3923-3934.2006",
language = "English",
volume = "80",
pages = "3923--3934",
journal = "Journal of Virology",
issn = "0022-538X",
publisher = "American Society for Microbiology",
number = "8",

}

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

VL - 80

SP - 3923

EP - 3934

JO - Journal of Virology

JF - Journal of Virology

SN - 0022-538X

IS - 8

ER -