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

Nature Immunology volume 3, pages 822–829 (2002)Cite this article

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 up-regulate 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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Figure 1: BLyS, APRIL, IL-4 and/or IL-10 induce CSR from Cμ to Cγ, Cα or Cε.
Figure 2: BLyS or APRIL and TGF-β induce CSR from Cμ to Cα.
Figure 3: CSR is induced by BLyS, APRIL or CD40L but not by TNF-α or LT-α.
Figure 4: BLyS or APRIL up-regulate multiple germline IH-CH and mature VHDH-CH transcripts.
Figure 5: BLyS or APRIL up-regulate both membrane-bound and secreted IgG and IgA.
Figure 6: Activated DCs induce CSR through BLyS and APRIL.
Figure 7: Activated monocytes induce CSR through BLyS and APRIL.
Figure 8: Activated DCs induce plasmacytoid differentiation through BLyS and APRIL.

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Acknowledgements

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.).

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  1. Division of Molecular Immunology, Department of Pathology and Laboratory Medicine, Joan and Sanford I. Weill Medical College of Cornell University, 1300 York Avenue, New York, 10021, NY, USA

    Mikhail B. Litinskiy, Bing He, Andras Schaffer, Paolo Casali & Andrea Cerutti

  2. Human Genome Sciences, 9410 Key West Avenue, Rockville, 20850, MD, USA

    Bernardetta Nardelli & David M. Hilbert

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  1. Mikhail B. Litinskiy
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Correspondence to Andrea Cerutti.

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B. N. and D. M. H. are employed by Human Genome Sciences.

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Litinskiy, M., Nardelli, B., Hilbert, D. et al. DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL. Nat Immunol 3, 822–829 (2002). https://doi.org/10.1038/ni829

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