DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation

作者：Jabara Haifa H; McDonald Douglas R; Janssen Erin; Massaad Michel J; Ramesh Narayanaswamy; Borzutzky Arturo; Rauter Ingrid; Benson Halli; Schneider Lynda; Baxi Sachin; Recher Mike; Notarangelo Luigi D; Wakim Rima; Dbaibo Ghassan; Dasouki Majed; Al Herz Waleed; Barlan Isil; Baris Safa; Kutukculer Necil; Ochs Hans D; Plebani Alessandro; Kanariou Maria; Lefranc Gerard; Reisli Ismail; Fitzgerald Katherine A; Golenbock Douglas; Manis John; Keles Sevgi; Ceja Reuben

来源：Nature Immunology, 2012, 13(6): 612-+.

DOI：10.1038/ni.2305

The adaptors DOCK8 and MyD88 have been linked to serological memory. Here we report that DOCK8-deficient patients had impaired antibody responses and considerably fewer CD27(+) memory B cells. B cell proliferation and immunoglobulin production driven by Toll-like receptor 9 (TLR9) were considerably lower in DOCK8-deficient B cells, but those driven by the costimulatory molecule CD40 were not. In contrast, TLR9-driven expression of AICDA (which encodes the cytidine deaminase AID), the immunoglobulin receptor CD23 and the costimulatory molecule CD86 and activation of the transcription factor NF-kappa B, the kinase p38 and the GTPase Rac1 were intact. DOCK8 associated constitutively with MyD88 and the tyrosine kinase Pyk2 in normal B cells. After ligation of TLR9, DOCK8 became tyrosine-phosphorylated by Pyk2, bound the Src-family kinase Lyn and linked TLR9 to a Src-kinase Syk-transcription factor STAT3 cascade essential for TLR9-driven B cell proliferation and differentiation. Thus, DOCK8 functions as an adaptor in a TLR9-MyD88 signaling pathway in B cells.

• 出版日期2012-6
• 单位河北医科大学