CEACAM1 mediates B cell aggregation in central nervous system autoimmunity
Rovituso DM, Scheffler L, Wunsch M, Kleinschnitz C, Doerck S, Ulzheimer J, Bayas A, Steinman L, Erguen S, Kuerten S (2016)
Publication Type: Journal article
Publication year: 2016
Journal
Book Volume: 6
Article Number: 29847
DOI: 10.1038/srep29847
Abstract
B cell aggregates in the central nervous system (CNS) have been associated with rapid disease progression in patients with multiple sclerosis (MS). Here we demonstrate a key role of carcinoembryogenic antigen-related cell adhesion molecule1 (CEACAM1) in B cell aggregate formation in MS patients and a B cell-dependent mouse model of MS. CEACAM1 expression was increased on peripheral blood B cells and CEACAM1 + B cells were present in brain infiltrates of MS patients. Administration of the anti-CEACAM1 antibody T84.1 was efficient in blocking aggregation of B cells derived from MS patients. Along these lines, application of the monoclonal anti-CEACAM1 antibody mCC1 was able to inhibit CNS B cell aggregate formation and significantly attenuated established MS-like disease in mice in the absence of any adverse effects. CEACAM1 was co-expressed with the regulator molecule T cell immunoglobulin and mucin domain-3 (TIM-3) on B cells, a novel molecule that has recently been described to induce anergy in T cells. Interestingly, elevated coexpression on B cells coincided with an autoreactive T helper cell phenotype in MS patients. Overall, these data identify CEACAM1 as a clinically highly interesting target in MS pathogenesis and open new therapeutic avenues for the treatment of the disease.
Authors with CRIS profile
Involved external institutions
Julius-Maximilians-Universität Würzburg
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Caritas-Krankenhaus Bad Mergentheim gemeinnützige GmbH
Germany (DE)
Klinikum Augsburg
Germany (DE)
Stanford University
United States (USA) (US)
Germany (DE)
Universitätsklinikum Würzburg
Germany (DE)
Caritas-Krankenhaus Bad Mergentheim gemeinnützige GmbH
Germany (DE)
Klinikum Augsburg
Germany (DE)
Stanford University
United States (USA) (US)
How to cite
APA:
Rovituso, D.M., Scheffler, L., Wunsch, M., Kleinschnitz, C., Doerck, S., Ulzheimer, J.,... Kuerten, S. (2016). CEACAM1 mediates B cell aggregation in central nervous system autoimmunity. Scientific Reports, 6. https://doi.org/10.1038/srep29847
MLA:
Rovituso, Damiano M., et al. "CEACAM1 mediates B cell aggregation in central nervous system autoimmunity." Scientific Reports 6 (2016).
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