Plasmacytoid dendritic cells regulate B-cell growth and differentiation via CD70.
The ability of plasmacytoid dendritic cells (pDCs) to promote plasma cell differentiation and immunoglobulin (Ig) secretion through the production of type I interferon and interleukin-6 has been well documented, although the role of additional 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 differentiation 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 contact between pDCs and B cells. CpG-stimulated pDCs can induce the proliferation 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 therefore identified CD70 as an important factor in the regulation of B-cell growth and differentiation by pDCs.
Department of Immunology, University of Texas, M. D. Anderson Cancer Center, Houston, TX 77030-1903, USA.
Joanne
J
Shaw
Yui-Hsi
YH
Wang
Tomoki
T
Ito
Kazuhiko
K
Arima
Yong-Jun
YJ
Liu
D000328:Adult; D000818:Animals; D019138:Antibodies, Blocking / Q000494:pharmacology; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D053282:CD27 Ligand / Q000276:immunology*; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D003713:Dendritic Cells / Q000166:cytology* / Q000276:immunology* / Q000378:metabolism; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects; D007370:Interferon Type I / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000378:metabolism
D019138:Antibodies, Blocking; D053282:CD27 Ligand; C408982:CPG-oligonucleotide; D007370:Interferon Type I; D009838:Oligodeoxyribonucleotides; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7