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

Nat Immunol. 2002 Sep;3(9):822-9. doi: 10.1038/ni829. Epub 2002 Aug 5.


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

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • B-Cell Activating Factor
  • CD40 Antigens / physiology*
  • Dendritic Cells / physiology*
  • Humans
  • Immunoglobulin A / biosynthesis
  • Immunoglobulin Class Switching / genetics*
  • Immunoglobulin G / biosynthesis
  • Immunoglobulin Heavy Chains / genetics
  • Lipopolysaccharides / pharmacology
  • Membrane Proteins / physiology*
  • NF-kappa B / metabolism
  • Neuropeptides / physiology*
  • Nuclear Proteins / physiology*
  • Receptors, Antigen, B-Cell / physiology
  • Recombination, Genetic
  • Tumor Necrosis Factor-alpha / physiology*
  • Up-Regulation


  • ANP32B protein, human
  • B-Cell Activating Factor
  • CD40 Antigens
  • Immunoglobulin A
  • Immunoglobulin G
  • Immunoglobulin Heavy Chains
  • Lipopolysaccharides
  • Membrane Proteins
  • NF-kappa B
  • Neuropeptides
  • Nuclear Proteins
  • Receptors, Antigen, B-Cell
  • TNFSF13B protein, human
  • Tumor Necrosis Factor-alpha