IMMUNOBIOLOGY Plasmacytoid dendritic cells regulate B-cell growth and differentiation via CD70

The ability of plasmacytoid dendritic cells (pDCs) to promote plasma cell differentia-tion and immunoglobulin (Ig) secretion through the production of type I inter-feron and interleukin-6 has been well documented, although the role of addi-tional factors, including tumor necrosis factor receptor-ligand interactions, has not been addressed. On stimulation with the Toll-like receptor ligand CpG (B type, 2006) we found that pDCs exhibit strong and stable expression of CD70, a tumor necrosis factor family ligand that binds to its receptor CD27 expressed on memory B cells and promotes plasma cell differen-tiation and Ig secretion. Using a pDC/B-cell coculture system, we found that CpG-stimulated pDCs can induce the proliferation of CD40L-activated human peripheral B cells and Ig secretion. This occurs independently of interferon and residual CpG, and requires physical con-tact between pDCs and B cells. CpG-stimulated pDCs can induce the prolifera-tion of both naive and memory B cells, although Ig secretion is restricted to the memory subset. Blocking the interaction of CD70 with CD27 using an antagonist anti-CD70 antibody reduces the induction of B-cell proliferation and IgG secretion by CpG-stimulated pDCs. We have there-fore identified CD70 as an important fac-tor in the regulation of B-cell growth and differentiation by pDCs. (Blood. 2010; 115(15):3051-3057