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B-cell epitope spre...
B-cell epitope spreading and inflammation in a mouse model of arthritis is associated with a deficiency in reactive oxygen species production
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- Khmaladze, Ia (author)
- Karolinska Institutet, Stockholm, Sweden
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- Saxena, Amit (author)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Nandakumar, Kutty Selva, 1965- (author)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden
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- Holmdahl, Rikard (author)
- Karolinska Institutet,Karolinska Institutet, Stockholm, Sweden; Southern Medical University, Guangzhou, China
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(creator_code:org_t)
- 2015-06-03
- 2015
- English.
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In: European Journal of Immunology. - Weinheim : Wiley-VCH Verlagsgesellschaft. - 0014-2980 .- 1521-4141. ; 45:8, s. 2243-2251
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Abstract
Subject headings
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- Autoantibody-mediated inflammation contributes to the development of rheumatoid arthritis (RA), and anti-type II collagen (CII) antibodies are present in the serum, synovial fluid, and cartilage of RA patients. We had previously generated and characterized knock-in mice expressing a germline-encoded, CII-specific IgH (B10Q.ACB), which demonstrated positive selection of self-reactive B cells. Here, we show that despite the spontaneous production of CII-specific autoantibodies, B10Q.ACB mice are protected from collagen-induced arthritis. Introducing a mutation in the Ncf1 gene, leading to ROS deficiency, breaks this strong arthritis resistance. Disease development in Ncf1-mutated B10Q.ACB mice is associated with an enhanced germinal center formation but without somatic mutations of the auto-reactive B cells, increased T-cell responses and intramolecular epitope-spreading. Thus, ROS-mediated B-cell tolerance to a self-antigen could operate by limiting the expansion of the auto-reactive B-cell repertoire, which has important implications for the understanding of epitope spreading phenomena in rheumatoid arthritis and other autoimmune diseases.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Reumatologi och inflammation (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Rheumatology and Autoimmunity (hsv//eng)
Keyword
- Arthritis
- Auto-reactive B cells
- Autoantibodies
- Epitope spreading
- ROS
Publication and Content Type
- ref (subject category)
- art (subject category)
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