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Functional anergy in a subpopulation of naive B cells from healthy humans that express autoreactive immunoglobulin receptors
- Source :
- The Journal of Experimental Medicine
- Publication Year :
- 2008
- Publisher :
- Rockefeller University Press, 2008.
-
Abstract
- Self-reactive B cells not controlled by receptor editing or clonal deletion may become anergic. We report that fully mature human B cells negative for surface IgM and retaining only IgD are autoreactive and functionally attenuated (referred to as naive IgD+IgM− B cells [BND]). These BND cells typically make up 2.5% of B cells in the peripheral blood, have antibody variable region genes in germline (unmutated) configuration, and, by all current measures, are fully mature. Analysis of 95 recombinant antibodies expressed from the variable genes of single BND cells demonstrated that they are predominantly autoreactive, binding to HEp-2 cell antigens and DNA. Upon B cell receptor cross-linkage, BND cells have a reduced capacity to mobilize intracellular calcium or phosphorylate tyrosines, demonstrating that they are anergic. However, intense stimulation causes BND cells to fully respond, suggesting that these cells could be the precursors of autoantibody secreting plasma cells in autoimmune diseases such as systemic lupus erythematosus or rheumatoid arthritis. This is the first identification of a distinct mature human B cell subset that is naturally autoreactive and controlled by the tolerizing mechanism of functional anergy.
- Subjects :
- Immunology
Naive B cell
B-cell receptor
B-Lymphocyte Subsets
Receptors, Antigen, B-Cell
Autoimmunity
Lymphocyte Activation
Autoantigens
Immunoglobulin D
Article
Clonal deletion
Immunophenotyping
03 medical and health sciences
0302 clinical medicine
Antigen
Antigens, CD
Humans
Immunology and Allergy
Calcium Signaling
Phosphorylation
030304 developmental biology
Clonal Anergy
0303 health sciences
Genes, Immunoglobulin
biology
Clonal anergy
Ionomycin
Antibodies, Monoclonal
Receptor editing
Articles
Antibodies, Anti-Idiotypic
3. Good health
B-1 cell
Kinetics
Immunoglobulin M
Antibodies, Antinuclear
Mutation
biology.protein
Tyrosine
030215 immunology
Subjects
Details
- ISSN :
- 15409538 and 00221007
- Volume :
- 206
- Database :
- OpenAIRE
- Journal :
- Journal of Experimental Medicine
- Accession number :
- edsair.doi.dedup.....f897e18c163d8067b492b6fbc940740b