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

• Published in: Nature immunology Vol. 3; no. 9; pp. 822 - 829
• Main Authors: Cerutti, Andrea, Litinskiy, Mikhail B, Nardelli, Bernardetta, Hilbert, David M, He, Bing, Schaffer, Andras, Casali, Paolo
• Format: Journal Article
• Language: English
• Published: United States Nature Publishing Group 01.09.2002
• Subjects: B-Cell Activating Factor; CD40 Antigens - physiology; Dendritic Cells - physiology; Deoxyribonucleic acid; DNA; Humans; Immunoglobulin A - biosynthesis; Immunoglobulin Class Switching - genetics; Immunoglobulin G - biosynthesis; Immunoglobulin Heavy Chains - genetics; Lipopolysaccharides - pharmacology; Membrane Proteins - physiology; Neuropeptides - physiology; NF-kappa B - metabolism; Nuclear Proteins - physiology; Receptors, Antigen, B-Cell - physiology; Recombination, Genetic; Tumor Necrosis Factor-alpha - physiology; Up-Regulation
• ISSN: 1529-2908; 1529-2916
• DOI: 10.1038/ni829

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.