Journal article
T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells
Immunity (Cambridge, Mass.), v 29(2), pp 249-260
15 Aug 2008
PMID: 18691914
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
On the lupus-prone MRL-lpr/lpr (MRL-lpr) background, AM14 rheumatoid factor (RF) B cells are activated, differentiate into plasmablasts, and undergo somatic hypermutation outside of follicles. Using multiple strategies to impair T cells, we found that such AM14 B cell activation did not require T cells but could be modulated by them. In vitro, the signaling adaptor MyD88 is required for IgG anti-chromatin to stimulate AM14 B cell proliferation when T cells are absent. However, the roles of Toll-like receptors (TLRs) in AM14 B cell activation in vivo have not been investigated. We found that activation, expansion, and differentiation of AM14 B cells depended on MyD88; however, mice lacking either TLR7 or TLR9 displayed partial defects, indicating complex roles for these receptors. T cell-independent activation of certain autoreactive B cells, which gain stimuli via endogenous TLR ligands instead of T cells, may be the initial step in the generation of canonical autoantibodies.
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Details
- Title
- T cell-independent and toll-like receptor-dependent antigen-driven activation of autoreactive B cells
- Creators
- Robin A. Herlands - Yale UniversitySean R. Christensen - Yale UniversityRebecca A. Sweet - Yale UniversityUri Hershberg - Yale UniversityMark J. Shlomchik - Yale University
- Publication Details
- Immunity (Cambridge, Mass.), v 29(2), pp 249-260
- Publisher
- Elsevier
- Number of pages
- 12
- Grant note
- R01AI073722 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) P01AR050256 / NATIONAL INSTITUTE OF ARTHRITIS AND MUSCULOSKELETAL AND SKIN DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Arthritis & Musculoskeletal & Skin Diseases (NIAMS) P01-AI36529; P01-AR050256 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000258610800013
- Scopus ID
- 2-s2.0-48749085121
- Other Identifier
- 991019280182804721
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- Web of Science research areas
- Immunology