Nature Immunology3, 822 - 829 (2002)
Published online: 5 August 2002; | doi:10.1038/ni829
DCs induce CD40-independent immunoglobulin class switching through BLyS and APRIL
Mikhail B. Litinskiy1, Bernardetta Nardelli2, David M. Hilbert2, Bing He1, Andras Schaffer1, Paolo Casali1
& Andrea Cerutti1
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, NY 10021, USA.
2
Human Genome Sciences, 9410 Key West Avenue, Rockville, MD 20850, USA.
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-, interferon- or CD40 ligand. In the presence of interleukin 10 (IL-10) or transforming growth factor-, BLyS and APRIL induce CSR from C to C and/or C genes in B cells, whereas CSR to C 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.
, interferon-
or CD40 ligand. In the presence of interleukin 10 (IL-10) or transforming growth factor-
, BLyS and APRIL induce CSR from C
to C
and/or C
genes in B cells, whereas CSR to C
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.
