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Pathogenic Autoreactive B Cells Are Not Negatively Selected toward Matrix Protein Collagen II.

Cao, Duojia ; Khmaladze, Ia ; Jia, Hongwei ; Bajtner, Estelle ; Kutty Selva, Nandakumar ; Blom, Thomas LU ; Mo, John A and Holmdahl, Rikard (2011) In Journal of immunology (Baltimore, Md. : 1950) 187. p.4451-4458
Abstract
We have addressed the importance of B cell tolerance to collagen type II, a matrix protein, which is a target in rheumatoid arthritis (RA) and its mouse models. We generated a germline-encoded anti-collagen type II (CII) IgH replacement anti-C1 B cell mouse strain (ACB) to investigate how B cell tolerance to CII, a matrix protein, is subverted and to further understand pathogenesis of RA. Phenotypic analysis revealed that CII-specific B cells were surprisingly neither deleted nor anergized. Instead, they were readily detected in all lymphoid organs. Spontaneously produced autoantibodies could bind directly to cartilage surface without detectable pathology. However, exaggerated arthritis was seen after injection of anti-CII Abs specific for... (More)
We have addressed the importance of B cell tolerance to collagen type II, a matrix protein, which is a target in rheumatoid arthritis (RA) and its mouse models. We generated a germline-encoded anti-collagen type II (CII) IgH replacement anti-C1 B cell mouse strain (ACB) to investigate how B cell tolerance to CII, a matrix protein, is subverted and to further understand pathogenesis of RA. Phenotypic analysis revealed that CII-specific B cells were surprisingly neither deleted nor anergized. Instead, they were readily detected in all lymphoid organs. Spontaneously produced autoantibodies could bind directly to cartilage surface without detectable pathology. However, exaggerated arthritis was seen after injection of anti-CII Abs specific for other epitopes. In addition, Abs from CII-specific hybridomas generated from ACB mice induced arthritis. Interestingly, IgH/L chain sequence data in B cell hybridomas revealed a lack of somatic mutations in autoreactive B cells. The ACB model provides the first possibility, to our knowledge, to study B cell tolerance to a matrix protein, and the observations made in the study could not be predicted from previous models. B cell-reactive epitopes on CII are largely shared between human RA and rodent CII-induced arthritis; this study, therefore, has important implications for further understanding of pathological processes in autoimmune diseases like RA. (Less)
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Contribution to journal
publication status
published
subject
in
Journal of immunology (Baltimore, Md. : 1950)
volume
187
pages
4451 - 4458
publisher
American Association of Immunologists
external identifiers
  • wos:000296496000010
  • pmid:21940677
  • scopus:80555154914
  • pmid:21940677
ISSN
1550-6606
DOI
10.4049/jimmunol.1101378
language
English
LU publication?
yes
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The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Faculty of Medicine (000022000), BMC Biomedical Centre (0130322000), Medical Inflammation Research (013212019)
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a57da59c-2e9d-4335-9092-229c351a8d48 (old id 2168656)
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http://www.ncbi.nlm.nih.gov/pubmed/21940677?dopt=Abstract
date added to LUP
2016-04-04 09:43:31
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2019-08-06 01:52:57
@article{a57da59c-2e9d-4335-9092-229c351a8d48,
  abstract     = {We have addressed the importance of B cell tolerance to collagen type II, a matrix protein, which is a target in rheumatoid arthritis (RA) and its mouse models. We generated a germline-encoded anti-collagen type II (CII) IgH replacement anti-C1 B cell mouse strain (ACB) to investigate how B cell tolerance to CII, a matrix protein, is subverted and to further understand pathogenesis of RA. Phenotypic analysis revealed that CII-specific B cells were surprisingly neither deleted nor anergized. Instead, they were readily detected in all lymphoid organs. Spontaneously produced autoantibodies could bind directly to cartilage surface without detectable pathology. However, exaggerated arthritis was seen after injection of anti-CII Abs specific for other epitopes. In addition, Abs from CII-specific hybridomas generated from ACB mice induced arthritis. Interestingly, IgH/L chain sequence data in B cell hybridomas revealed a lack of somatic mutations in autoreactive B cells. The ACB model provides the first possibility, to our knowledge, to study B cell tolerance to a matrix protein, and the observations made in the study could not be predicted from previous models. B cell-reactive epitopes on CII are largely shared between human RA and rodent CII-induced arthritis; this study, therefore, has important implications for further understanding of pathological processes in autoimmune diseases like RA.},
  author       = {Cao, Duojia and Khmaladze, Ia and Jia, Hongwei and Bajtner, Estelle and Kutty Selva, Nandakumar and Blom, Thomas and Mo, John A and Holmdahl, Rikard},
  issn         = {1550-6606},
  language     = {eng},
  pages        = {4451--4458},
  publisher    = {American Association of Immunologists},
  series       = {Journal of immunology (Baltimore, Md. : 1950)},
  title        = {Pathogenic Autoreactive B Cells Are Not Negatively Selected toward Matrix Protein Collagen II.},
  url          = {http://dx.doi.org/10.4049/jimmunol.1101378},
  doi          = {10.4049/jimmunol.1101378},
  volume       = {187},
  year         = {2011},
}