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10.4049/jimmunol.1401723

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C4201975!4201975!25252961
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suck abstract from ncbi


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pmid25252961      J+Immunol 2014 ; 193 (9): 4312-21
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  • Siglecs induce tolerance to cell surface antigens by BIM-dependent deletion of the antigen-reactive B cells #MMPMID25252961
  • Macauley MS; Paulson JC
  • J Immunol 2014[Nov]; 193 (9): 4312-21 PMID25252961show ga
  • Infusion of blood cells from a donor can induce humoral tolerance in a recipient and increase the probability of successful organ transplant; a clinical method defined as donor-specific transfusion (DST). Despite the clinical success of DST, the immunological mechanism(s) by which blood cells displaying a foreign antigen induce tolerance remain poorly understood. Based on recent findings showing that the B cell siglecs, CD22 and Siglec-G, can promote tolerance to antigens presented on the same surface as their ligands, we speculated that the B cell siglecs are key players in tolerance induced by DST. Using a variety of chemical and genetic approaches, we show that the B cell siglecs mediate tolerance to cell surface antigens by initiating an inhibitory signal that culminates in elimination of the antigen-reactive B cell. CD22 and Siglec-G are recruited to the immunological synapse by sialic acid ligands on the antigen-bearing cells, producing a tolerogenic signal involving Lyn and the pro-apoptotic factor BIM that promotes deletion of the B cell and failure of mice to develop antibodies to the antigen upon subsequent challenge. We speculate that this tolerogenic mechanism is a contributing factor in DST and a mechanism of peripheral B cell tolerance to cell surface autoantigens.
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