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Molnarfi, N.* ; Schulze-Topphoff, U.* ; Weber, M.S.* ; Patarroyo, J.C.* ; Prod'homme, T.* ; Varrin-Doyer, M.* ; Shetty, A.* ; Linington, C.* ; Slavin, A.J.* ; Hidalgo, J.* ; Jenne, D. ; Wekerle, H.* ; Sobel, R.A.* ; Bernard, C.C.* ; Shlomchik, M.J.* ; Zamvil, S.S.*

MHC class II-dependent B cell APC function is required for induction of CNS autoimmunity independent of myelin-specific antibodies.

J. Exp. Med. 210, 2921-2937 (2013)
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Whether B cells serve as antigen-presenting cells (APCs) for activation of pathogenic T cells in the multiple sclerosis model experimental autoimmune encephalomyelitis (EAE) is unclear. To evaluate their role as APCs, we engineered mice selectively deficient in MHC II on B cells (B-MHC II(-/-)), and to distinguish this function from antibody production, we created transgenic (Tg) mice that express the myelin oligodendrocyte glycoprotein (MOG)-specific B cell receptor (BCR; IgH(MOG-mem)) but cannot secrete antibodies. B-MHC II(-/-) mice were resistant to EAE induced by recombinant human MOG (rhMOG), a T cell- and B cell-dependent autoantigen, and exhibited diminished Th1 and Th17 responses, suggesting a role for B cell APC function. In comparison, selective B cell IL-6 deficiency reduced EAE susceptibility and Th17 responses alone. Administration of MOG-specific antibodies only partially restored EAE susceptibility in B-MHC II(-/-) mice. In the absence of antibodies, IgH(MOG-mem) mice, but not mice expressing a BCR of irrelevant specificity, were fully susceptible to acute rhMOG-induced EAE, also demonstrating the importance of BCR specificity. Spontaneous opticospinal EAE and meningeal follicle-like structures were observed in IgH(MOG-mem) mice crossed with MOG-specific TCR Tg mice. Thus, B cells provide a critical cellular function in pathogenesis of central nervous system autoimmunity independent of their humoral involvement, findings which may be relevant to B cell-targeted therapies.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Experimental Allergic Encephalomyelitis; Central-nervous-system; Progressive Multiple-sclerosis; Cd4(+) T-cells; Oligodendrocyte Glycoprotein; Monoclonal-antibody; Transgenic Mice; Lymphocyte-t; Mouse Model; Antigen
ISSN (print) / ISBN 0022-1007
e-ISSN 1540-9538
Zeitschrift Journal of Experimental Medicine
Quellenangaben Band: 210, Heft: 13, Seiten: 2921-2937 Artikelnummer: , Supplement: ,
Verlag Rockefeller University Press
Begutachtungsstatus