Rauter, IngridRecher, MikeWakim, RimaDbaibo, GhassanDasouki, MajedBarlan, IsilBaris, SafaKutukculer, NecilOchs, HansPlebani, AlessandroKanariou, MariaLefranc, GerardReisli, IsmailFitzgerald, KaterineGolenbock, DouglasKeles, SevgiCeja, ReubenJabara, Haifa HalimMcDonald, DouglasJanssen, ErinMassaad, MichelRamesh, NarayanaswamyBorzutzky, ArturoBenson, Halli LouiseSchneider, LyndaBaxi, SachinNotarangelo, LuigiAl-Herz, WaleedManis, JohnChatila, TalalGeha, Raif2013-05-032012Jabara, Haifa Halim, Douglas Ray McDonald, Erin Margaret Janssen, Michel Massaad, Narayanaswamy Ramesh, Arturo Borzutzky, Ingrid Rauter, et al. 2012. DOCK8 functions as an adaptor that links TLR–MyD88 signaling to B cell activation. Nature immunology 13(6): 612-620.1529-29081529-2916http://nrs.harvard.edu/urn-3:HUL.InstRepos:10610336DOCK8 and MyD88 have been implicated in serologic memory. Here we report antibody responses were impaired and \(CD27^+\) memory B cells were severely reduced in DOCK8-deficient patients. Toll-like receptor 9 (TLR9)- but not CD40-driven B cell proliferation and immunoglobulin production were severely reduced in DOCK8-deficient B cells. In contrast, TLR9-driven expression of AICDA, CD23 and CD86, and activation of NF-κB, p38 and Rac1 were intact. DOCK8 associated constitutively with MyD88 and the tyrosine kinase Pyk2 in normal B cells. Following TLR9 ligation, DOCK8 became tyrosine phosphorylated by Pyk2, bound the Src family kinase Lyn and linked TLR9 to a Src-Syk-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.en-USJournal Article2013-05-0310.1038/ni.2305