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-alpha, interferon-gamma or CD40 ligand. In the presence of interleukin 10 (IL-10) or transforming growth factor-beta, BLyS and APRIL induce CSR from C(mu) to C(gamma) and/or C(alpha) genes in B cells, whereas CSR to C(epsilon) 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.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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B-Cell Activating Factor
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CD40 Antigens / physiology*
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Dendritic Cells / physiology*
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Humans
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Immunoglobulin A / biosynthesis
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Immunoglobulin Class Switching / genetics*
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Immunoglobulin G / biosynthesis
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Immunoglobulin Heavy Chains / genetics
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Lipopolysaccharides / pharmacology
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Membrane Proteins / physiology*
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NF-kappa B / metabolism
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Neuropeptides / physiology*
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Nuclear Proteins / physiology*
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Receptors, Antigen, B-Cell / physiology
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Recombination, Genetic
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Tumor Necrosis Factor-alpha / physiology*
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Up-Regulation
Substances
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ANP32B protein, human
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B-Cell Activating Factor
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CD40 Antigens
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Immunoglobulin A
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Immunoglobulin G
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Immunoglobulin Heavy Chains
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Lipopolysaccharides
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Membrane Proteins
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NF-kappa B
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Neuropeptides
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Nuclear Proteins
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Receptors, Antigen, B-Cell
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TNFSF13B protein, human
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Tumor Necrosis Factor-alpha