NDLI: SLAP deficiency decreases dsDNA autoantibody production.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Peterson, Lisa K. Pennington, Luke F. Shaw, Laura A. Brown, Meredith Treacy, Eric C. Friend, Samantha F. Hatlevik, Øyvind Rubtsova, Kira Rubtsov, Anatoly V. Dragone, Leonard L.
Description	Country affiliation: United States Author Affiliation: Peterson LK ( Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.); Pennington LF ( Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.); Shaw LA ( Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.); Brown M ( Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.); Treacy EC ( Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.); Friend SF ( Department of Pediatrics, University of Colorado Denver, 13001 E. 17th Place, Aurora, CO 80045, USA); Hatlevik Ø ( Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.); Rubtsova K ( Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.); Rubtsov AV ( Department of Immunology, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA.); Dragone LL ( Department of Pediatrics, National Jewish Health, 1400 Jackson Street, Denver, CO 80206, USA)
Abstract	Src-like adaptor protein (SLAP) adapts c-Cbl, an E3 ubiquitin ligase, to activated components of the BCR signaling complex regulating BCR levels and signaling in developing B cells. Based on this function, we asked whether SLAP deficiency could decrease the threshold for tolerance and eliminate development of autoreactive B cells in two models of autoantibody production. First, we sensitized mice with a dsDNA mimetope that causes an anti-dsDNA response. Despite equivalent production of anti-peptide antibodies compared to BALB/c controls, SLAP(-/-) mice did not produce anti-dsDNA. Second, we used the 56R tolerance model. SLAP(-/-) 56R mice had decreased levels of dsDNA-reactive antibodies compared to 56R mice due to skewed light chain usage. Thus, SLAP is a critical regulator of B-cell development and function and its deficiency leads to decreased autoreactive B cells that are otherwise maintained by inefficient receptor editing or failed negative selection.
File Format	HTM / HTML
ISSN	15216616
e-ISSN	15217035
DOI	10.1016/j.clim.2013.12.007
Journal	Clinical Immunology
Issue Number	2
Volume Number	150
Language	English
Publisher	Elsevier
Publisher Date	2014-02-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Immunology Antibodies, Antinuclear Biosynthesis Immunology Proto-oncogene Proteins Pp60(c-src) Deficiency Animals B-lymphocyte Subsets Metabolism Immunoglobulin Heavy Chains Immunoglobulin Kappa-chains Immunoglobulin Lambda-chains Mice Mice, Knockout Genetics Receptors, Antigen, B-cell Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology

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SLAP deficiency decreases dsDNA autoantibody production

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Src-like adaptor protein (SLAP) regulates B cell receptor levels in a c-Cbl-dependent manner

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