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

Duojia Cao, Ia Khmaladze, Hongwei Jia, Estelle Bajtner, Nandakumar Kutty Selva, Thomas Blom, John A Mo, Rikard Holmdahl

Research output: Contribution to journalArticlepeer-review

15 Citations (SciVal)

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.
Original languageEnglish
Pages (from-to)4451-4458
JournalJournal of immunology (Baltimore, Md. : 1950)
Volume187
DOIs
Publication statusPublished - 2011

Bibliographical note

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)

Subject classification (UKÄ)

  • Immunology in the medical area

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