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Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis

Cellular & Molecular Immunology volume 8, pages 296–304 (2011)Cite this article

Abstract

Antibodies against type II collagen (CII) are essential for development of collagen-induced arthritis (CIA), but how and where the B-cell response to CII is initiated is not fully known. We show here that naive DBA/1 mice display naturally reactive IgM and IgG anti-CII producing B cells prior to immunization. The CII-reactive B cells were observed in the spleen and recognized as marginal zone (MZ) B cells. After CII immunization, CII-specific B cells expanded rapidly in the spleen, in contrast to the lymph nodes, with the initial response derived from MZ B cells and later by follicular (FO) B cells. This was evident despite that the MZ B cells were subject to stringent tolerance mechanisms by having a greater Fc gamma receptor IIb expression than the FO B cells. Further, the MZ B cells migrated to the FO areas upon immunization, possibly providing antigen and activating FO T cells and subsequently FO B cells. Thus, around CIA onset increased numbers of IgG anti-CII producing FO B cells was seen in the spleen, which was dominated by IgG2a- and IgG2b-positive cells. These data demonstrate that CII-reactive MZ B cells are present before and expand after CII immunization, suggesting an initiating role of MZ B cells in the development of CIA.

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Acknowledgements

This research project was supported by the Swedish Research Council and The King Gustav V's 80 years Foundation. For technical assistance, we would like to thank Dr Jan Grawé at the Cell Analysis Core Facility (Rudbeck Laboratory, Uppsala University) for cell sorting, Julie Moran (Department of Cell and Molecular Immunology, Uppsala University) for ELISpot, Sara Lind (Karolinska Institute, Solna) for FACS and finally Professor Birgitta Heyman, Dr Magnus Åbrink (Department of Medical Biochemistry and Microbiology, Uppsala University) and Professor Stellan Sandler (Department of Medical Cell Biology, Uppsala University) for providing the Balb/c, C57BL/6 and NOD mice.

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Author notes

  1. Cecilia Carnrot and Kajsa E Prokopec: These authors contributed equally to this work.

Authors and Affiliations

  1. Department of Cell and Molecular Biology, Uppsala University, Uppsala, Sweden

    Cecilia Carnrot, Kajsa E Prokopec, Kristina Råsbo & Sandra Kleinau

  2. Department of Medicine, Unit of Clinical Allergy Research, The Karolinska Institute, Solna, Sweden

    Kajsa E Prokopec & Mikael CI Karlsson

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  1. Cecilia Carnrot
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Correspondence to Sandra Kleinau.

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Carnrot, C., Prokopec, K., Råsbo, K. et al. Marginal zone B cells are naturally reactive to collagen type II and are involved in the initiation of the immune response in collagen-induced arthritis. Cell Mol Immunol 8, 296–304 (2011). https://doi.org/10.1038/cmi.2011.2

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