CEACAM1 mediates B cell aggregation in central nervous system autoimmunity

• Published in: Scientific reports Vol. 6; no. 1; p. 29847
• Main Authors: Rovituso, Damiano M., Scheffler, Laura, Wunsch, Marie, Kleinschnitz, Christoph, Dörck, Sebastian, Ulzheimer, Jochen, Bayas, Antonios, Steinman, Lawrence, Ergün, Süleyman, Kuerten, Stefanie
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 20.07.2016; Nature Publishing Group
• Subjects: 13/1; 13/106; 13/51; 14/63; 45/77; 631/250/38; 631/378/371; 692/617/375/1666; Aggregates; Animals; Antibodies; Antibodies, Anti-Idiotypic - administration & dosage; Antigens, CD - genetics; Antigens, CD - immunology; Autoimmunity - genetics; B-Lymphocytes - metabolism; Cell Adhesion - genetics; Cell Adhesion - immunology; Cell Adhesion Molecules - antagonists & inhibitors; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - immunology; Cell Aggregation - genetics; Cell Aggregation - immunology; Cells; Central nervous system; Central Nervous System - metabolism; Central Nervous System - pathology; Disease; Disease Models, Animal; Gene Expression Regulation - genetics; Gene Expression Regulation - immunology; Humanities and Social Sciences; Humans; Immunoglobulins; Lymphatic system; Lymphocyte Activation - genetics; Mice; multidisciplinary; Multiple Sclerosis - genetics; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Nervous system; Neurology; Proteins; Science; Germany
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep29847

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.