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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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author
organization
publishing date
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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
ISSN
1550-6606
DOI
10.4049/jimmunol.1101378
language
English
LU publication?
yes
id
a57da59c-2e9d-4335-9092-229c351a8d48 (old id 2168656)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/21940677?dopt=Abstract
date added to LUP
2011-10-03 13:05:04
date last changed
2017-09-17 08:46:25
@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},
  volume       = {187},
  year         = {2011},
}