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10.1016/j.jaci.2013.10.051 http://scihub22266oqcxt.onion/10.1016/j.jaci.2013.10.051 C4077428!4077428!24373350     free     free     free Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 231.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Deprecated: Implicit conversion from float 265.2 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534       J+Allergy+Clin+Immunol 2014 ; 133 (4): 1149-61 Nephropedia Template TP {{tp|p=24373350|t=2014. Signaling Lymphocyte Activated Molecule (SLAM)/SLAM-associated Protein (SAP) Pathway Regulates Human B-cell Tolerance |pdf=|usr=}}{{24373350}} gab.com Text Signaling Lymphocyte Activated Molecule (SLAM)/SLAM-associated Protein (SAP) Pathway Regulates Human B-cell Tolerance JO: J Allergy Clin Immunol http://www.kidney.de/pget.php?&tw=1&pmid=24373350 #FOAvip Background: SAP can mediate the function of SLAM molecules, which have been proposed to be involved in the development of autoimmunity in mice. Objective: We sought to determine if the SLAM/SAP pathway regulates the establishment of human B-cell tolerance and what mechanisms of B-cell tolerance could be affected by SAP deficiency. Methods: We tested the reactivity of antibodies isolated from single B cells from SAP-deficient X-linked lymphoproliferative disease (XLP) patients. The expressions of SAP and SLAM family members were assessed in human bone marrow developing B cells. We also analyzed regulatory T cell (Treg) function in XLP patients and healthy controls. Results: We found that new emigrant/transitional B cells from XLP patients were enriched in autoreactive clones, revealing a defective central B-cell tolerance checkpoint in the absence of functional SAP. In agreement with a B-cell intrinsic regulation of central tolerance, we identified SAP expression in a discrete subset of bone marrow immature B cells. SAP colocalized with SLAMF6 only in association with clustered B-cell receptors (BCRs) likely recognizing self-antigens, suggesting that SLAM/SAP regulate BCR-mediated central tolerance. In addition, XLP patients displayed defective peripheral B-cell tolerance, which is normally controlled by Tregs. Tregs in XLP patients seem functional but SAP-deficient T cells were resistant to Treg-mediated suppression. Indeed, SAP-deficient T cells were hyper-responsive to TCR stimulation, which resulted in increased secretion of interleukin-2, IFN? and TNF?. Conclusions: SAP expression is required for the counterselection of developing autoreactive B cells and prevents their T-cell dependent accumulation in the periphery. Twit Text FOAVip Signaling Lymphocyte Activated Molecule (SLAM)/SLAM-associated Protein (SAP) Pathway Regulates Human B-cell Tolerance ????J Allergy Clin Immunol http://www.kidney.de/pget.php?&tw=1&pmid=24373350 #FOAvip Twit Text # Free Paper on # # # # # LINK http://www.kidney.de/pget.php?&tw=1&pmid=24373350 #FOAvip English Wikipedia <ref>{{Cite pmid|24373350}}</ref> Signaling Lymphocyte Activated Molecule (SLAM)/SLAM-associated Protein (SAP) Pathway Regulates Human B-cell Tolerance #MMPMID24373350 Menard L; Cantaert T; Chamberlain N; Tangye SG; Riminton S; Church JA; Klion A; Cunninham-Rundles C; Nichols KE; Meffre E J Allergy Clin Immunol 2014[Apr]; 133 (4): 1149-61 PMID24373350show ga Background: SAP can mediate the function of SLAM molecules, which have been proposed to be involved in the development of autoimmunity in mice. Objective: We sought to determine if the SLAM/SAP pathway regulates the establishment of human B-cell tolerance and what mechanisms of B-cell tolerance could be affected by SAP deficiency. Methods: We tested the reactivity of antibodies isolated from single B cells from SAP-deficient X-linked lymphoproliferative disease (XLP) patients. The expressions of SAP and SLAM family members were assessed in human bone marrow developing B cells. We also analyzed regulatory T cell (Treg) function in XLP patients and healthy controls. Results: We found that new emigrant/transitional B cells from XLP patients were enriched in autoreactive clones, revealing a defective central B-cell tolerance checkpoint in the absence of functional SAP. In agreement with a B-cell intrinsic regulation of central tolerance, we identified SAP expression in a discrete subset of bone marrow immature B cells. SAP colocalized with SLAMF6 only in association with clustered B-cell receptors (BCRs) likely recognizing self-antigens, suggesting that SLAM/SAP regulate BCR-mediated central tolerance. In addition, XLP patients displayed defective peripheral B-cell tolerance, which is normally controlled by Tregs. Tregs in XLP patients seem functional but SAP-deficient T cells were resistant to Treg-mediated suppression. Indeed, SAP-deficient T cells were hyper-responsive to TCR stimulation, which resulted in increased secretion of interleukin-2, IFN? and TNF?. Conclusions: SAP expression is required for the counterselection of developing autoreactive B cells and prevents their T-cell dependent accumulation in the periphery. äSignaling Lymphocyte Activated Molecule (SLAM)/SLAM-associated Protein(epmc).pdf DeepDyve Pubget Overpricing