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Decoration of T-independent antigen with ligands for CD22 and Siglec-G can suppress immunity and induce B cell tolerance in vivo.
- Source :
-
The Journal of experimental medicine [J Exp Med] 2010 Jan 18; Vol. 207 (1), pp. 173-87. Date of Electronic Publication: 2009 Dec 28. - Publication Year :
- 2010
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Abstract
- Autoreactive B lymphocytes first encountering self-antigens in peripheral tissues are normally regulated by induction of anergy or apoptosis. According to the "two-signal" model, antigen recognition alone should render B cells tolerant unless T cell help or inflammatory signals such as lipopolysaccharide are provided. However, no such signals seem necessary for responses to T-independent type 2 (TI-2) antigens, which are multimeric antigens lacking T cell epitopes and Toll-like receptor ligands. How then do mature B cells avoid making a TI-2-like response to multimeric self-antigens? We present evidence that TI-2 antigens decorated with ligands of inhibitory sialic acid-binding Ig-like lectins (siglecs) are poorly immunogenic and can induce tolerance to subsequent challenge with immunogenic antigen. Two siglecs, CD22 and Siglec-G, contributed to tolerance induction, preventing plasma cell differentiation or survival. Although mutations in CD22 and its signaling machinery have been associated with dysregulated B cell development and autoantibody production, previous analyses failed to identify a tolerance defect in antigen-specific mutant B cells. Our results support a role for siglecs in B cell self-/nonself-discrimination, namely suppressing responses to self-associated antigens while permitting rapid "missing self"-responses to unsialylated multimeric antigens. The results suggest use of siglec ligand antigen constructs as an approach for inducing tolerance.
- Subjects :
- Animals
Antibody Formation physiology
Autoantibodies genetics
Autoantibodies immunology
Autoantigens genetics
Cell Differentiation genetics
Cell Differentiation immunology
Cell Survival genetics
Cell Survival immunology
Inflammation genetics
Inflammation immunology
Lectins genetics
Ligands
Mice
Mice, Knockout
Plasma Cells cytology
Receptors, Antigen, B-Cell genetics
Sialic Acid Binding Ig-like Lectin 2 genetics
Sialic Acid Binding Immunoglobulin-like Lectins
T-Lymphocytes, Helper-Inducer cytology
T-Lymphocytes, Helper-Inducer immunology
Autoantigens immunology
Immune Tolerance physiology
Lectins immunology
Plasma Cells immunology
Receptors, Antigen, B-Cell immunology
Sialic Acid Binding Ig-like Lectin 2 immunology
Signal Transduction immunology
Subjects
Details
- Language :
- English
- ISSN :
- 1540-9538
- Volume :
- 207
- Issue :
- 1
- Database :
- MEDLINE
- Journal :
- The Journal of experimental medicine
- Publication Type :
- Academic Journal
- Accession number :
- 20038598
- Full Text :
- https://doi.org/10.1084/jem.20091873