The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online March 24, 2008
doi:10.1084/jem.20072619
The Journal of Experimental Medicine, Vol. 205, No. 4, 853-868
The Rockefeller University Press, 0022-1007 $30.00
© 2008 Weber et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Supplemental Material Index
Right arrow Correction
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Google Scholar
Right arrow Articles by Weber, M.
Right arrow Articles by Batista, F. D.
PubMed
Right arrow PubMed Citation
Right arrow Articles by Weber, M.
Right arrow Articles by Batista, F. D.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

ARTICLE

 Phospholipase C-{gamma}2 and Vav cooperate within signaling microclusters to propagate B cell spreading in response to membrane-bound antigen

Michele Weber1, Bebhinn Treanor1, David Depoil1, Hisaaki Shinohara2, Naomi E. Harwood1, Masaki Hikida2, Tomohiro Kurosaki2, and Facundo D. Batista1

1 Lymphocyte Interaction Laboratory, London Research Institute, Cancer Research UK, London WC2A 3PX, England, UK
2 Laboratory for Lymphocyte Differentiation, RIKEN Research Center for Allergy and Immunology, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan

CORRESPONDENCE Facundo D. Batista: facundo.batista{at}cancer.org.uk

B cell receptor (BCR) recognition of membrane-bound antigen initiates a spreading and contraction response, the extent of which is controlled through the formation of signaling-active BCR-antigen microclusters and ultimately affects the outcome of B cell activation. We followed a genetic approach to define the molecular requirements of BCR-induced spreading and microcluster formation. We identify a key role for phospholipase C-{gamma}2 (PLC{gamma}2), Vav, B cell linker, and Bruton's tyrosine kinase in the formation of highly coordinated "microsignalosomes," the efficient assembly of which is absolutely dependent on Lyn and Syk. Using total internal reflection fluorescence microscopy, we examine at high resolution the recruitment of PLC{gamma}2 and Vav to microsignalosomes, establishing a novel synergistic relationship between the two. Thus, we demonstrate the importance of cooperation between components of the microsignalosome in the amplification of signaling and propagation of B cell spreading, which is critical for appropriate B cell activation.

Abbreviations used: BCAP, B cell adaptor for PI3K; Blnk, B cell linker; Btk, Bruton's tyrosine kinase; cSMAC, central supramolecular activation cluster; DIC, differential interference contrast; EGFP, enhanced GFP; GEF, guanine nucleotide exchange factor; HEL, hen egg lysozyme; IP3, inositol 1,4,5-triphosphate; IRM, interference reflection microscopy; IS, immunological synapse; PI3K, phosphoinositide 3-kinase; PIP2, phosphatidylinositol bisphosphate; PKCβ, protein kinase C-β; PLC{gamma}2, phospholipase C-{gamma}2; PLC{gamma}2-LD, PLC{gamma}2 with lipase-defective activity; SEM, scanning electron microscopy; SH2, Src homology 2; TIRFM, total internal reflection fluorescence microscopy; Vav1/2-KO, Vav1 and Vav2 knockout.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS