DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL.
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.
Litinskiy
Mikhail B
MB
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, NY 10021, USA.
Nardelli
Bernardetta
B
Hilbert
David M
DM
He
Bing
B
Schaffer
Andras
A
Casali
Paolo
P
Cerutti
Andrea
A
D053264:B-Cell Activating Factor; D019013:CD40 Antigens / Q000502:physiology*; D003713:Dendritic Cells / Q000502:physiology*; D006801:Humans; D007070:Immunoglobulin A / Q000096:biosynthesis; D017578:Immunoglobulin Class Switching / Q000235:genetics*; D007074:Immunoglobulin G / Q000096:biosynthesis; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D008070:Lipopolysaccharides / Q000494:pharmacology; D008565:Membrane Proteins / Q000502:physiology*; D016328:NF-kappa B / Q000378:metabolism; D009479:Neuropeptides / Q000502:physiology*; D009687:Nuclear Proteins / Q000502:physiology*; D011947:Receptors, Antigen, B-Cell / Q000502:physiology; D011995:Recombination, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology*; D015854:Up-Regulation
C490341:ANP32B protein, human; D053264:B-Cell Activating Factor; D019013:CD40 Antigens; D007070:Immunoglobulin A; D007074:Immunoglobulin G; D007143:Immunoglobulin Heavy Chains; D008070:Lipopolysaccharides; D008565:Membrane Proteins; D016328:NF-kappa B; D009479:Neuropeptides; D009687:Nuclear Proteins; D011947:Receptors, Antigen, B-Cell; C505719:TNFSF13B protein, human; D014409:Tumor Necrosis Factor-alpha