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DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL
Mikhail B Litinskiy1, Bernardetta Nardelli, David M Hilbert
1Division 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.
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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.