Work

Siglecs Induce Tolerance to Cell Surface Antigens by BIM-Dependent Deletion of the Antigen-Reactive B Cells

Year: 2014

Type: article

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.

Source: The Journal of Immunology

DOI: 10.4049/jimmunol.1401723

Authors: Matthew S Macauley, James C Paulson

Institution: Scripps Research Institute

Language: English

Topic: T-cell and B-cell Immunology

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: green

Funders: Department of Science and Technology, Ministry of Science and Technology, India, National Institute of Allergy and Infectious Diseases