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

Nature Immunology
Haifa H JabaraRaif S Geha

Abstract

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.

References

Jan 1, 1989·Journal of Clinical Immunology·C Cunningham-Rundles
Jul 22, 1999·Clinical Immunology : the Official Journal of the Clinical Immunology Society·C Cunningham-Rundles, C Bodian
Jan 7, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G Hartmann, A M Krieg
Jan 21, 2000·The Journal of Immunology : Official Journal of the American Association of Immunologists·G HartmannA M Krieg
Mar 8, 2000·Cellular Signalling·H AvrahamS Avraham
Mar 10, 2001·The Journal of Immunology : Official Journal of the American Association of Immunologists·J F ArrighiC Hauser
Dec 31, 2002·Biochemical and Biophysical Research Communications·Cédric BoudotEmmanuelle Petitfrère
Feb 14, 2004·The Journal of Biological Chemistry·Chong-Shan Shi, John H Kehrl
Oct 19, 2004·Oncogene·Stephen B Gauld, John C Cambier
Jun 11, 2005·Annals of Allergy, Asthma & Immunology : Official Publication of the American College of Allergy, Asthma, & Immunology·Francisco A BonillaUNKNOWN Joint Council of Allergy, Asthma and Immunology
Aug 6, 2005·Vaccine·Risini D WeeratnaHeather L Davis
Sep 6, 2005·International Immunology·Maria Dolores GallegoRaif S Geha
Oct 29, 2005·Journal of Cell Science·Nahum MellerChittibabu Guda
Nov 18, 2005·Nature·Chandrashekhar Pasare, Ruslan Medzhitov
Jan 21, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Charlotte Cunningham-RundlesAtsushi Nakazawa
Apr 4, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Heath M GuayEva Szomolanyi-Tsuda
Jun 9, 2007·European Journal of Immunology·Nora KatsenelsonMustafa Akkoyunlu
Jun 19, 2007·Nature Immunology·Eicke LatzDouglas T Golenbock
Sep 4, 2007·Trends in Cell Biology·Jean-François Côté, Kristiina Vuori
Nov 28, 2007·The Journal of Experimental Medicine·Almut Meyer-BahlburgDavid J Rawlings
Mar 21, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Sean A DiehlHergen Spits
Feb 14, 2009·PLoS Pathogens·Edward P Browne, Dan R Littman
Apr 30, 2009·Journal of Leukocyte Biology·L GiordaniM Viora
Jun 27, 2009·Nature Reviews. Immunology·Gregory M Barton, Jonathan C Kagan
Sep 25, 2009·The New England Journal of Medicine·Qian ZhangHelen C Su
Dec 4, 2009·Journal of Leukocyte Biology·Cai-Xia XiWen-Cheng Xiong
Dec 17, 2009·The Journal of Allergy and Clinical Immunology·Karin R EngelhardtTalal A Chatila
Feb 2, 2010·Journal of Proteomics·Peter C BonnetteLeonard Buckbinder
Feb 6, 2010·Proceedings of the National Academy of Sciences of the United States of America·Fatih M UckunZahide Ozer
May 15, 2010·Nature Reviews. Immunology·Attila MócsaiVictor L J Tybulewicz
Aug 24, 2010·Immunological Reviews·Taketoshi YoshidaBimba F Hoyer

❮ Previous
Next ❯

Citations

Aug 6, 2013·Experimental Cell Research·Akihiko NishikimiYoshinori Fukui
May 23, 2012·Nature Immunology·Markus Werner, Hassan Jumaa
Oct 10, 2013·Current Opinion in Hematology·Austen J J WorthPaul Veys
Dec 6, 2012·Arthritis Research & Therapy·Patrick F K YongBodo Grimbacher
Jan 10, 2013·Annual Review of Immunology·Luigi D Notarangelo
Mar 13, 2014·Journal of Clinical Immunology·John RoutesTroy Torgerson
Aug 6, 2014·Nature Communications·Akhilesh K SinghMohamed Oukka
Jul 23, 2014·Journal of Interferon & Cytokine Research : the Official Journal of the International Society for Interferon and Cytokine Research·Brendan John Jenkins
Jul 16, 2014·Cytokine & Growth Factor Reviews·Saurabh Chattopadhyay, Ganes C Sen
Oct 31, 2014·Cellular and Molecular Life Sciences : CMLS·Audrey Le Floc'h, Morgan Huse
Jan 24, 2016·Clinical Immunology : the Official Journal of the Clinical Immunology Society·W J M JanssenM Boes
May 15, 2015·International Reviews of Immunology·Trine H Mogensen
Feb 18, 2016·The Journal of Allergy and Clinical Immunology·Shaheen KhanM Teresa de la Morena
Mar 8, 2013·The Journal of Allergy and Clinical Immunology·Luigi D Notarangelo
Apr 27, 2012·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Waleed Al-HerzRaif S Geha
Nov 26, 2015·Pediatric Allergy and Immunology : Official Publication of the European Society of Pediatric Allergy and Immunology·Beate HaglEllen D Renner
Oct 20, 2015·The Journal of Allergy and Clinical Immunology·Christina S YeeJanet Chou
Oct 20, 2015·The Journal of Allergy and Clinical Immunology·Henner MorbachEric Meffre
Mar 23, 2015·Allergologia et immunopathologia·S Gutierrez-HincapiéC M Trujillo-Vargas
Jan 29, 2014·European Journal of Immunology·Saskia ZieglerIsabelle Bekeredjian-Ding
May 12, 2015·European Journal of Immunology·Guanjun DongYayi Hou
May 23, 2014·Immunologic Research·Claire M Buchta, Gail A Bishop
Jul 19, 2013·European Journal of Haematology·Beáta TóthLászló Maródi
Oct 15, 2013·Immunological Reviews·Dale A MouldingAdrian J Thrasher
Oct 15, 2013·Biological Reviews of the Cambridge Philosophical Society·Elena S GusarevaMarie Lipoldová
Apr 17, 2014·European Journal of Immunology·Bi-Sheng LiuRene E M Toes
Feb 1, 2015·Biology of Blood and Marrow Transplantation : Journal of the American Society for Blood and Marrow Transplantation·Jennifer Cuellar-RodriguezDennis D Hickstein
Apr 29, 2014·The Journal of Allergy and Clinical Immunology·Sevgi KelesTalal A Chatila
May 7, 2014·The Journal of Allergy and Clinical Immunology·Huie JingHelen C Su
Sep 15, 2015·The Journal of Clinical Investigation·Francesca PalaEric Meffre
Jul 12, 2013·Mediators of Inflammation·Abhishek ShastriUday Kishore
Sep 16, 2014·European Journal of Pharmacology·Ling-Jun Ho, Jenn-Haung Lai
Apr 20, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Daifulah Al-ZahraniRaif Geha
Jul 16, 2014·Progress in Retinal and Eye Research·Kazuhiko NamekataTakayuki Harada
Mar 1, 2015·The Journal of Allergy and Clinical Immunology·Karin R EngelhardtBodo Grimbacher
Jun 18, 2015·The New England Journal of Medicine·Kerry DobbsLuigi D Notarangelo
Dec 30, 2014·Cellular and Molecular Life Sciences : CMLS·Mariann KremlitzkaAnna Erdei
Apr 22, 2015·Immunology and Cell Biology·Vanessa L Bryant, Charlotte A Slade
Jan 21, 2014·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Erin JanssenRaif S Geha
Jul 31, 2013·Clinical Immunology : the Official Journal of the Clinical Immunology Society·Daan J aan de KerkTaco W Kuijpers

❮ Previous
Next ❯

Methods Mentioned

BETA
GTPase
FCS
ELISA
flow
electrophoresis
PCR
immunoprecipitation
pull-down

Software Mentioned

Adobe Photoshop
elements
CellQuest
FlowJo
NIS
NIH Image

Related Concepts

Related Feeds

B cell Activation

B cell activation is initiated by the ligation of the B cell receptor with antigen and ultimately results in the production of protective antibodies against potentially pathogenic invaders. Here is the latest research.