DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL

Mikhail B. Litinskiy; Bernardetta Nardelli; David M. Hilbert; Bing He; Andras Schaffer; Paolo Casali; Andrea Cerutti

doi:10.1038/ni829

DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL

Mikhail B. Litinskiy, Bernardetta Nardelli, David M. Hilbert, Bing He, Andras Schaffer, Paolo Casali, Andrea Cerutti

Research output: Contribution to journal › Article › peer-review

1089 Scopus citations

Abstract

Immunoglobulin (Ig) class-switch DNA recombination (CSR) is thought to be highly dependent upon engagement of CD40 on B cells by CD40 ligand on T cells. We show here that dendritic cells upregulate BLyS and APRIL upon exposure to interferon-α, interferon-γ or CD40 ligand. In the presence of interleukin 10 (IL- 10) or transforming growth factor-β, BLyS and APRIL induce CSR from C_μ to C_γ and/or C_α genes in B cells, whereas CSR to C_ε requires IL-4. Secretion of class-switched antibodies requires additional stimulation by B cell antigen receptor engagement and IL-15. By eliciting CD40-independent Ig class switching and plasmacytoid differentiation, BLyS and APRIL critically link the innate and adaptive immune responses.

Original language	English (US)
Pages (from-to)	822-829
Number of pages	8
Journal	Nature Immunology
Volume	3
Issue number	9
DOIs	https://doi.org/10.1038/ni829
State	Published - Sep 2002
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1038/ni829

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title = "DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL",

abstract = "Immunoglobulin (Ig) class-switch DNA recombination (CSR) is thought to be highly dependent upon engagement of CD40 on B cells by CD40 ligand on T cells. We show here that dendritic cells upregulate BLyS and APRIL upon exposure to interferon-α, interferon-γ or CD40 ligand. In the presence of interleukin 10 (IL- 10) or transforming growth factor-β, BLyS and APRIL induce CSR from Cμ to Cγ and/or Cα genes in B cells, whereas CSR to Cε requires IL-4. Secretion of class-switched antibodies requires additional stimulation by B cell antigen receptor engagement and IL-15. By eliciting CD40-independent Ig class switching and plasmacytoid differentiation, BLyS and APRIL critically link the innate and adaptive immune responses.",

author = "Litinskiy, {Mikhail B.} and Bernardetta Nardelli and Hilbert, {David M.} and Bing He and Andras Schaffer and Paolo Casali and Andrea Cerutti",

note = "Funding Information: Acknowledgments We thank K. S. Picha (Immunex Corp.) for recombinant soluble CD40L and S. Narula (Schering-Plough) for IL-4 and IL-10. Supported by a New Investigator Grant from The Leukemia Research Foundation (to A. C.), research grants from The SLE Foundation (to A. C. and P. C.) and grants from the National Institutes of Health AR 47872 (to A. C.),AR 40908 and AI 45011 (to P. C.).",

year = "2002",

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doi = "10.1038/ni829",

language = "English (US)",

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AU - Litinskiy, Mikhail B.

AU - Nardelli, Bernardetta

AU - Hilbert, David M.

AU - He, Bing

AU - Schaffer, Andras

AU - Casali, Paolo

AU - Cerutti, Andrea

N1 - Funding Information: Acknowledgments We thank K. S. Picha (Immunex Corp.) for recombinant soluble CD40L and S. Narula (Schering-Plough) for IL-4 and IL-10. Supported by a New Investigator Grant from The Leukemia Research Foundation (to A. C.), research grants from The SLE Foundation (to A. C. and P. C.) and grants from the National Institutes of Health AR 47872 (to A. C.),AR 40908 and AI 45011 (to P. C.).

PY - 2002/9

Y1 - 2002/9

N2 - Immunoglobulin (Ig) class-switch DNA recombination (CSR) is thought to be highly dependent upon engagement of CD40 on B cells by CD40 ligand on T cells. We show here that dendritic cells upregulate BLyS and APRIL upon exposure to interferon-α, interferon-γ or CD40 ligand. In the presence of interleukin 10 (IL- 10) or transforming growth factor-β, BLyS and APRIL induce CSR from Cμ to Cγ and/or Cα genes in B cells, whereas CSR to Cε requires IL-4. Secretion of class-switched antibodies requires additional stimulation by B cell antigen receptor engagement and IL-15. By eliciting CD40-independent Ig class switching and plasmacytoid differentiation, BLyS and APRIL critically link the innate and adaptive immune responses.

AB - Immunoglobulin (Ig) class-switch DNA recombination (CSR) is thought to be highly dependent upon engagement of CD40 on B cells by CD40 ligand on T cells. We show here that dendritic cells upregulate BLyS and APRIL upon exposure to interferon-α, interferon-γ or CD40 ligand. In the presence of interleukin 10 (IL- 10) or transforming growth factor-β, BLyS and APRIL induce CSR from Cμ to Cγ and/or Cα genes in B cells, whereas CSR to Cε requires IL-4. Secretion of class-switched antibodies requires additional stimulation by B cell antigen receptor engagement and IL-15. By eliciting CD40-independent Ig class switching and plasmacytoid differentiation, BLyS and APRIL critically link the innate and adaptive immune responses.

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DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL

Abstract

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