Epitopes described in "Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression."

Article Authors:Takashi Matsushita; Koichi Yanaba; Jean-David Bouaziz; Manabu Fujimoto; Thomas F Tedder
Article Title:Regulatory B cells inhibit EAE initiation in mice while other B cells promote disease progression.
Reference Detail
Reference ID:1025930
Abstract:EAE is a mouse T cell-mediated autoimmune disease of the CNS used to model the human condition MS. The contributions of B cells to EAE initiation and progression are unclear. In this study, we have shown that EAE disease initiation and progression are differentially influenced by the depletion of B cells from mice with otherwise intact immune systems. CD20 antibody-mediated B cell depletion before EAE induction substantially exacerbated disease symptoms and increased encephalitogenic T cell influx into the CNS. Increased symptom severity resulted from the depletion of a rare IL-10-producing CD1dhiCD5+ regulatory B cell subset (B10 cells), since the adoptive transfer of splenic B10 cells before EAE induction normalized EAE in B cell-depleted mice. While transfer of regulatory B10 cells was maximally effective during early EAE initiation, they had no obvious role during disease progression. Rather, B cell depletion during EAE disease progression dramatically suppressed symptoms. Specifically, B cells were required for the generation of CD4+ T cells specific for CNS autoantigen and the entry of encephalitogenic T cells into the CNS during disease progression. These results demonstrate reciprocal regulatory roles for B cells during EAE immunopathogenesis. The therapeutic effect of B cell depletion for the treatment of autoimmunity may therefore depend on the relative contributions and the timing of these opposing B cell activities during the course of disease initiation and pathogenesis.
Affiliations:Department of Immunology, Duke University Medical Center, Durham, North Carolina, USA.
Reference Type:Literature
PubMed ID:18802481
Journal:J Clin Invest
Journal Volume:118
Article Pages:3420-30
Journal ISSN:0021-9738
Article Chemical List:Antibodies, Monoclonal;Antigens, CD20;Interleukin-10
Article MeSH List:Animals; Antibodies, Monoclonal(immunology); Antigens, CD20(immunology); B-Lymphocytes(immunology); CD4-Positive T-Lymphocytes(immunology); Cell Proliferation; Central Nervous System(cytology); Disease Progression; Encephalomyelitis, Autoimmune, Experimental(immunology; physiopathology; therapy); Female; Interleukin-10(immunology); Lymphocyte Depletion; Mice; Mice, Inbred C57BL; Spleen(cytology); T-Lymphocytes(cytology; immunology)
Curation Last Updated:2015-07-30 20:47:38