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dc.contributor.authorRauter, Ingrid
dc.contributor.authorRecher, Mike
dc.contributor.authorWakim, Rima
dc.contributor.authorDbaibo, Ghassan
dc.contributor.authorDasouki, Majed
dc.contributor.authorBarlan, Isil
dc.contributor.authorBaris, Safa
dc.contributor.authorKutukculer, Necil
dc.contributor.authorOchs, Hans
dc.contributor.authorPlebani, Alessandro
dc.contributor.authorKanariou, Maria
dc.contributor.authorLefranc, Gerard
dc.contributor.authorReisli, Ismail
dc.contributor.authorFitzgerald, Katerine
dc.contributor.authorGolenbock, Douglas
dc.contributor.authorKeles, Sevgi
dc.contributor.authorCeja, Reuben
dc.contributor.authorJabara, Haifa Halim
dc.contributor.authorMcDonald, Douglas Ray
dc.contributor.authorJanssen, Erin Margaret
dc.contributor.authorMassaad, Michel
dc.contributor.authorRamesh, Narayanaswamy
dc.contributor.authorBorzutzky, Arturo
dc.contributor.authorBenson, Halli Louise
dc.contributor.authorSchneider, Lynda C.
dc.contributor.authorBaxi, Sachin
dc.contributor.authorNotarangelo, Luigi D.
dc.contributor.authorAl-Herz, Waleed
dc.contributor.authorManis, John P.
dc.contributor.authorChatila, Talal Amine
dc.contributor.authorGeha, Raif Salim
dc.date.accessioned2013-05-03T13:03:51Z
dc.date.issued2012
dc.identifier.citationJabara, 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.en_US
dc.identifier.issn1529-2908en_US
dc.identifier.issn1529-2916en_US
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:10610336
dc.description.abstractDOCK8 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_US
dc.language.isoen_USen_US
dc.publisherNature Publishing Groupen_US
dc.relation.isversionofdoi:10.1038/ni.2305en_US
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC3362684/pdf/en_US
dash.licenseLAA
dc.titleDOCK8 Functions as an Adaptor that Links TLR–MyD88 Signaling to B Cell Activationen_US
dc.typeJournal Articleen_US
dc.description.versionAccepted Manuscripten_US
dc.relation.journalNature Immunologyen_US
dash.depositing.authorJabara, Haifa Halim
dc.date.available2013-05-03T13:03:51Z
dc.identifier.doi10.1038/ni.2305*
dash.authorsorderedfalse
dash.contributor.affiliatedAl-Herz, Waleed
dash.contributor.affiliatedBenson, Halli Louise
dash.contributor.affiliatedJabara, Haifa Halim
dash.contributor.affiliatedMcDonald, Douglas
dash.contributor.affiliatedGeha, Raif
dash.contributor.affiliatedBorzutzky, Arturo
dash.contributor.affiliatedJanssen, Erin
dash.contributor.affiliatedRamesh, Narayanaswamy
dash.contributor.affiliatedChatila, Talal
dash.contributor.affiliatedSchneider, Lynda
dash.contributor.affiliatedMassaad, Michel
dash.contributor.affiliatedNotarangelo, Luigi
dash.contributor.affiliatedBaxi, Sachin
dash.contributor.affiliatedManis, John


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