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Titolo:
A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficientmice
Autore:
Hasegawa, M; Fujimoto, M; Poe, JC; Steeber, DA; Lowell, CA; Tedder, TF;
Indirizzi:
Duke Univ, Med Ctr, Dept Immunol, Durham, NC 27710 USA Duke Univ Durham NC USA 27710 Med Ctr, Dept Immunol, Durham, NC 27710 USA Univ Calif San Francisco, Dept Lab Med, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
JOURNAL OF IMMUNOLOGY
fascicolo: 5, volume: 167, anno: 2001,
pagine: 2469 - 2478
SICI:
0022-1767(20010901)167:5<2469:ACSPRA>2.0.ZU;2-S
Fonte:
ISI
Lingua:
ENG
Soggetto:
CELL ANTIGEN RECEPTOR; PROTEIN-TYROSINE KINASES; B-LYMPHOCYTE DEVELOPMENT; SRC-FAMILY; PHOSPHATIDYLINOSITOL 3-KINASE; TRANSDUCTION MOLECULE; NEGATIVE REGULATOR; CD19; ACTIVATION; COMPLEX;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Tedder, TF Duke Univ, Med Ctr, Dept Immunol, Box 3010, Durham, NC 27710 USA Duke Univ Box 3010 Durham NC USA 27710 10, Durham, NC 27710 USA
Citazione:
M. Hasegawa et al., "A CD19-dependent signaling pathway regulates autoimmunity in Lyn-deficientmice", J IMMUNOL, 167(5), 2001, pp. 2469-2478

Abstract

CD19 and the Src family protein tyrosine kinases (PTKs) are important regulators of intrinsic signaling thresholds in B cells. Regulation is achievedby cross-talk between Src family PTKs and CD19; Lyn is essential for CD19 phosphorylation, while CD19 establishes an Src family PTK activation loop that amplifies kinase activity. However, CD19-deficient (CD19(-/-)) B cells are hyporesponsive to transmembrane signals, while Lyn-deficient (Lyn(-/-))B cells exhibit a hyper-responsive phenotype resulting in autoimmunity. Toidentify the outcome of interactions between CD19 and Src family PTKs in vivo, B cell function was examined in mice deficient for CD19 and Lyn (CD19/Lyn(-/-)). Remarkably, CD19 deficiency suppressed the hyper-responsive phenotype of Lyn(-/-) B cells and autoimmunity characterized by serum autoantibodies and immune complex-mediated glomerulonephritis in Lyn(-/-) mice. Consistent with Lyn and CD19 each regulating conventional B cell development, BI cell development was markedly reduced by Lyn deficiency, with further reductions in the absence of CD19 expression. Tyrosine phosphorylation of Fyn and other cellular proteins induced following B cell Ag receptor ligation was dramatically reduced in CD19/Lyn(-/-) B cells relative to Lyn(-/-) B cells, while Syk phosphorylation was normal. In addition, the enhanced intracellular Ca2+ responses following B cell Ag receptor ligation that typify Lyndeficiency were delayed by the loss of CD19 expression. BCR-induced proliferation and Immoral immune responses were also markedly inhibited by CD19/Lyn deficiency. These findings demonstrate that while the CD19/Lyn amplification loop is a major regulator of signal transduction thresholds in B lymphocytes, CD19 regulation of other Src family PTKs also influences B cell function and the development of autoimmunity.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 09:38:00