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

Abstract

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 upregulate BLyS and APRIL upon exposure to interferon-α, interferon-γ or CD40 ligand. In the presence of interleukin 10 (IL- 10) or transforming growth factor-β, BLyS and APRIL induce CSR from Cμ to Cγ and/or Cα genes in B cells, whereas CSR to Cε 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.