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J Immunol. 2014 Nov 1;193(9):4312-21. doi: 10.4049/jimmunol.1401723. Epub 2014 Sep 24.

Siglecs induce tolerance to cell surface antigens by BIM-dependent deletion of the antigen-reactive B cells.

Author information

1
Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037; and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037.
2
Department of Cell and Molecular Biology, The Scripps Research Institute, La Jolla, CA 92037; Department of Immunology and Microbial Science, The Scripps Research Institute, La Jolla, CA 92037; and Department of Chemical Physiology, The Scripps Research Institute, La Jolla, CA 92037 jpaulson@scripps.edu.

Abstract

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 mechanisms by which blood cells displaying a foreign Ag induce tolerance remain poorly understood. Based on recent findings showing that the B cell siglecs, CD22 and Siglec-G, can promote tolerance to Ags 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 Ags by initiating an inhibitory signal that culminates in elimination of the Ag-reactive B cell. CD22 and Siglec-G are recruited to the immunological synapse by sialic acid ligands on the Ag-bearing cells, producing a tolerogenic signal involving Lyn and the proapoptotic factor BIM that promotes deletion of the B cell and failure of mice to develop Abs to the Ag 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.

PMID:
25252961
PMCID:
PMC4201975
DOI:
10.4049/jimmunol.1401723
[Indexed for MEDLINE]
Free PMC Article

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