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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
immunology and microbiology
DOCK8 functions as an adaptor that links TLR-MyD88 signaling to B cell activation
Nature Immunology, Volume 13, No. 6, Year 2012
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Description
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-κB, 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. © 2012 Nature America, Inc. All rights reserved.
Authors & Co-Authors
Jabara, Haifa H.
United States, Boston
Harvard Medical School
McDonald, Douglas R.
United States, Boston
Harvard Medical School
Janssen, Erin M.
United States, Boston
Harvard Medical School
Massaad, Michel J.
United States, Boston
Harvard Medical School
Ramesh, Narayanaswamy
United States, Boston
Harvard Medical School
Borzutzky, Arturo
United States, Boston
Harvard Medical School
Rauter, Ingrid
United States, Boston
Harvard Medical School
Benson, Halli
United States, Boston
Harvard Medical School
Schneider, Lynda C.
United States, Boston
Harvard Medical School
Baxi, Sachin N.
United States, Boston
Harvard Medical School
Recher, Mike
United States, Boston
Harvard Medical School
Notarangelo, Luigi Daniele
United States, Boston
Harvard Medical School
Hanna-Wakim, Rima
Lebanon, Beirut
American University of Beirut
Dbaibo, Ghassan S.
Lebanon, Beirut
American University of Beirut
Dasouki, Majed Jamil
United States, Kansas City
University of Kansas Medical Center
Al-Herz, Waleed
Kuwait
Al-sabah Hospital
Barlan, Işıl Berat
Turkey, Istanbul
Marmara Üniversitesi
Bariş, Safa
Turkey, Istanbul
Marmara Üniversitesi
Kütükçüler, Necil
Turkey, Izmir
Ege Üniversitesi
Ochs, Hans Dieter
United States, Seattle
University of Washington
Plebani, Alessandro
Italy, Brescia
Università Degli Studi Di Brescia
Kanariou, Maria G.
Greece, Athens
Aghia Sophia Children's Hospital
Lefranc, Gérard
France, Montpellier
Igh Institut de Génétique Humaine
Reisli, Ïsmail
Turkey, Selçuklu
Selçuk Üniversitesi
Fitzgerald, Katherine A.
United States, Worcester
University of Massachusetts Chan Medical School
Golenbock, Douglas
United States, Worcester
University of Massachusetts Chan Medical School
Manis, John P.
United States, Boston
Boston Children's Hospital
Keleş, Sevgi
Turkey, Selçuklu
Selçuk Üniversitesi
United States, Los Angeles
University of California, Los Angeles
Ceja, Reuben
United States, Los Angeles
University of California, Los Angeles
Chatila, T.
United States, Los Angeles
University of California, Los Angeles
Geha, Raif S.
United States, Boston
Harvard Medical School
Statistics
Citations: 138
Authors: 31
Affiliations: 14
Identifiers
Doi:
10.1038/ni.2305
ISSN:
15292908
e-ISSN:
15292916