Journal article
Anti-Chromatin Antibodies Drive In Vivo Antigen-Specific Activation and Somatic Hypermutation of Rheumatoid Factor B cells at Extrafollicular Sites
European journal of immunology, v 37(12), pp 3339-3351
01 Dec 2007
PMID: 18034429
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
A dominant type of spontaneous autoreactive B cell activation in murine lupus is the extrafollicular generation of plasmablasts. The factors governing such activation have been difficult to identify due to the stochastic onset and chronic nature of the response. Thus, the ability to induce a similar autoreactive B cell response with a known autoantigen
in vivo
would be a powerful tool in deciphering how autoimmune responses are initiated. We report here the establishment and characterization of a system to initiate autoreactive extrafollicular B cell responses that closely mirror the spontaneous response using IgG anti-chromatin Abs. We demonstrate that exogenously administered anti-chromatin Ab, presumably by forming immune complexes (ICs) with released nuclear material, drives activation of RF B cells in AM14 Tg mice. Anti-chromatin elicits autoreactive B cell activation and development into AFCs at the T-zone/red pulp border. Plasmablast generation occurs equally in BALB/c, MRL/+ and MRL/lpr mice, indicating that an autoimmune-prone genetic background is not required for the induced response. Importantly, infused IgG anti-chromatin induces somatic hypermutation (SHM) in the absence of a GC response, thus proving the extrafollicular SHM pathway. This system provides a window on the initiation of an autoantibody response and reveals authentic initiators of it.
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Details
- Title
- Anti-Chromatin Antibodies Drive In Vivo Antigen-Specific Activation and Somatic Hypermutation of Rheumatoid Factor B cells at Extrafollicular Sites
- Creators
- Robin A. Herlands - Yale UniversityJacqueline William - Yale UniversityUri Hershberg - Yale UniversityMark J. Shlomchik - Yale University
- Publication Details
- European journal of immunology, v 37(12), pp 3339-3351
- Publisher
- Wiley
- Grant note
- R01 AI061090 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID R01 AI073722 || AI / National Institute of Allergy and Infectious Diseases Extramural Activities : NIAID
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000251956800011
- Scopus ID
- 2-s2.0-37549049335
- Other Identifier
- 991019280040804721
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Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Immunology