Distinct Roles for Bruton's Tyrosine Kinase in B Cell Immune Synapse Formation.

Frontiers in Immunology
Sara Roman-GarciaYolanda R Carrasco

Abstract

Bruton's tyrosine kinase (Btk) has a key role in the signaling pathways of receptors essential for the B lymphocyte response. Given its implication in B cell-related immunodeficiencies, leukemias/lymphomas and autoimmunity, Btk is studied intensely and is a target for therapy. Here, using primary B cells from distinct mouse models and the pharmacological inhibitors ibrutinib and acalabrutinib, we report distinct roles for Btk in antigen-triggered immune synapse (IS) formation. Btk recruitment to the plasma membrane regulates the B cell ability to trigger IS formation as well as its appropriate molecular assembly; Btk shuttling/scaffold activities seem more relevant than the kinase function on that. Btk-kinase activity controls antigen accumulation at the IS through the PLCγ2/Ca2+ axis. Impaired Btk membrane-recruitment or kinase function likewise alters antigen-triggered microtubule-organizing center (MTOC) polarization to the IS, B cell activation and proliferation. Data also show that, for B cell function, IS architecture is as important as the quantity of antigen that accumulates at the synapse.

References

Nov 12, 2003·The Journal of Experimental Medicine·Marcel SpaargarenSteven T Pals
Mar 3, 2004·Molecular and Cellular Biology·Michael G TomlinsonArthur Weiss
Jun 15, 2004·Nature·Constantina BakolitsaRobert C Liddington
Apr 18, 2006·Trends in Cell Biology·Kun LingRichard A Anderson
Dec 7, 2007·The Journal of Cell Biology·Jonathan D HumphriesChristoph Ballestrem
Dec 26, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Shruti SharmaWenxia Song
Mar 18, 2009·Immunological Reviews·Tomohiro Kurosaki, Masaki Hikida
Apr 22, 2009·The Journal of Immunology : Official Journal of the American Association of Immunologists·Andrew J GrossAnthony L DeFranco
Jul 10, 2010·Proceedings of the National Academy of Sciences of the United States of America·Lee A HonigbergJoseph J Buggy
Jul 27, 2010·European Journal of Cell Biology·Alex Carisey, Christoph Ballestrem
Nov 5, 2010·Cold Spring Harbor Perspectives in Biology·Naomi E Harwood, Facundo D Batista
May 31, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Chaohong LiuWenxia Song
Jun 11, 2011·Blood·Julia Sáez de GuinoaYolanda R Carrasco
Nov 10, 2011·The Journal of Immunology : Official Journal of the American Association of Immunologists·Spencer A FreemanMichael R Gold
Jul 23, 2013·The Journal of Immunology : Official Journal of the American Association of Immunologists·Julia Saez de GuinoaYolanda R Carrasco
Mar 25, 2014·Nature Reviews. Cancer·Rudi W HendriksLaurens P Kil
Jun 16, 2015·Frontiers in Immunology·Maria-Isabel Yuseff, Ana Maria Lennon-Duménil
Aug 13, 2015·Cellular and Molecular Life Sciences : CMLS·Loretta TuostoRicciarda Galandrini
Sep 6, 2015·Current Topics in Microbiology and Immunology·Odilia B J CornethRudi W Hendriks
Dec 8, 2015·The New England Journal of Medicine·John C ByrdRichard R Furman

❮ Previous
Next ❯

Citations

Apr 16, 2020·Journal of Leukocyte Biology·Yolanda R Carrasco
Mar 18, 2021·Biophysical Journal·Alexandra ZakJulien Husson
Nov 21, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Lindsay E NyhoffPeggy L Kendall

❮ Previous
Next ❯

Methods Mentioned

BETA
FCS
FACS
flow cytometry
Protein Assay
GTPase
confocal microscopy
GTPases

Software Mentioned

FlowJo
Imaris
CellVue
GraphPad Prism
FiJi

Related Concepts

Related Feeds

Brain developing: Influences & Outcomes

This feed focuses on influences that affect the developing brain including genetics, fetal development, prenatal care, and gene-environment interactions. Here is the latest research in this field.

Autoimmune Diseases

Autoimmune diseases occur as a result of an attack by the immune system on the body’s own tissues resulting in damage and dysfunction. There are different types of autoimmune diseases, in which there is a complex and unknown interaction between genetics and the environment. Discover the latest research on autoimmune diseases here.

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.

B-Cell Leukemia (Keystone)

B-cell leukemia includes various types of lymphoid leukemia that affect B cells. Here is the latest research on B-cell leukemia.