The JI PBL Intereron Source
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     
 

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fujimoto, M.
Right arrow Articles by Tedder, T. F.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fujimoto, M.
Right arrow Articles by Tedder, T. F.
Right arrowPubmed/NCBI databases
*Compound via MeSH
*Substance via MeSH
Hazardous Substances DB
*CALCIUM COMPOUNDS
*CALCIUM, ELEMENTAL
*L-TYROSINE
The Journal of Immunology, 2002, 168: 5465-5476.
Copyright © 2002 by The American Association of Immunologists

Complementary Roles for CD19 and Bruton’s Tyrosine Kinase in B Lymphocyte Signal Transduction1

Manabu Fujimoto*, Jonathan C. Poe*, Anne B. Satterthwaite{dagger}, Matthew I. Wahl{dagger}, Owen N. Witte{dagger},{ddagger} and Thomas F. Tedder2,*

* Department of Immunology, Duke University Medical Center, Durham, NC 27710; and {dagger} Department of Microbiology and Molecular Genetics and {ddagger} Howard Hughes Medical Institute, University of California, Los Angeles, CA 90095

CD19 and Bruton’s tyrosine kinase (Btk) may function along common signaling pathways in regulating intrinsic and B cell Ag receptor (BCR)-induced signals. To identify physical and functional interactions between CD19 and Btk, a CD19-negative variant of the A20 B cell line was isolated, and CD19-deficient (CD19-/-) and CD19-overexpressing mice with the X-linked immunodeficient (Xid; Btk) mutation were generated. In A20 cells, Btk physically associated with CD19 following BCR engagement. CD19 and Btk interactions were not required for initial Btk phosphorylation, but CD19 expression maintained Btk in an activated state following BCR engagement. In primary B cells, CD19 signaling also required downstream Btk function since CD19-induced intracellular Ca2+ ([Ca2+]i) responses were modest in Xid B cells. In addition, CD19 overexpression did not normalize the Xid phenotype and most phenotypic and functional hallmarks of CD19 overexpression were not evident in these mice. However, CD19 and Btk also regulate independent signaling pathways since their combined loss had additive inhibitory effects on BCR-induced [Ca2+]i responses and CD19 deficiency induced a severe immunodeficiency in Xid mice. Thus, CD19 expression amplifies or prolongs Btk-mediated signaling, rather than serving as a required agent for Btk activation. Consistent with this, phosphatidylinositol 3-monophosphate kinase and Akt activation were normal in CD19-/- B cells following IgM engagement, although their kinetics of activation was altered. Thus, these biochemical and compound gene dosage studies indicate that Btk activation and [Ca2+]i responses following BCR engagement are regulated through multiple pathways, including a CD19/Src family kinase-dependent pathway that promotes the longevity of Btk signaling.




This article has been cited by other articles:


Home page
 BloodHome page
Y. Aiba, M. Kameyama, T. Yamazaki, T. F. Tedder, and T. Kurosaki
Regulation of B-cell development by BCAP and CD19 through their binding to phosphoinositide 3-kinase
Blood, February 1, 2008; 111(3): 1497 - 1503.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
R. Watanabe, M. Fujimoto, N. Ishiura, Y. Kuwano, H. Nakashima, N. Yazawa, H. Okochi, S. Sato, T. F. Tedder, and K. Tamaki
CD19 Expression in B Cells Is Important for Suppression of Contact Hypersensitivity
Am. J. Pathol., August 1, 2007; 171(2): 560 - 570.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Cell. Biol.Home page
Y. J. Kim, F. Sekiya, B. Poulin, Y. S. Bae, and S. G. Rhee
Mechanism of B-Cell Receptor-Induced Phosphorylation and Activation of Phospholipase C-{gamma}2
Mol. Cell. Biol., November 15, 2004; 24(22): 9986 - 9999.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Pathol.Home page
N. Asano, M. Fujimoto, N. Yazawa, S. Shirasawa, M. Hasegawa, H. Okochi, K. Tamaki, T. F. Tedder, and S. Sato
B Lymphocyte Signaling Established by the CD19/CD22 Loop Regulates Autoimmunity in the Tight-Skin Mouse
Am. J. Pathol., August 1, 2004; 165(2): 641 - 650.
[Abstract] [Full Text] [PDF]

Home page
 Proc. Natl. Acad. Sci. USAHome page
L. D. Wang, J. Lopes, A. B. Cooper, M. Dang-Lawson, L. Matsuuchi, and M. R. Clark
Selection of B lymphocytes in the periphery is determined by the functional capacity of the B cell antigen receptor
PNAS, January 27, 2004; 101(4): 1027 - 1032.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
D. C. Otero and R. C. Rickert
CD19 Function in Early and Late B Cell Development. II. CD19 Facilitates the Pro-B/Pre-B Transition
J. Immunol., December 1, 2003; 171(11): 5921 - 5930.
[Abstract] [Full Text] [PDF]

Home page
 J. Exp. Med.Home page
M. Spaargaren, E. A. Beuling, M. L. Rurup, H. P. Meijer, M. D. Klok, S. Middendorp, R. W. Hendriks, and S. T. Pals
The B Cell Antigen Receptor Controls Integrin Activity through Btk and PLC{gamma}2
J. Exp. Med., November 17, 2003; 198(10): 1539 - 1550.
[Abstract] [Full Text] [PDF]

Home page
 J. Immunol.Home page
T. Yokozeki, K. Adler, D. Lankar, and C. Bonnerot
B Cell Receptor-Mediated Syk-Independent Activation of Phosphatidylinositol 3-Kinase, Ras, and Mitogen-Activated Protein Kinase Pathways
J. Immunol., August 1, 2003; 171(3): 1328 - 1335.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
This Website Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.
All Contents Copyright © 2002 by The American Association of Immunologists, Inc. All rights reserved.