title: Cytokine-Defined B Cell Responses as Therapeutic Targets in Multiple Sclerosis.
abstract: Important antibody-independent pathogenic roles of B cells are emerging in autoimmune diseases, including multiple sclerosis (MS). The contrasting results of different treatments targeting B cells in patients (in spite of predictions of therapeutic benefits from animal models) call for a better understanding of the multiple roles that distinct human B cell responses likely play in MS. In recent years, both murine and human B cells have been identified with distinct functional properties related to their expression of particular cytokines. These have included regulatory (Breg) B cells (secreting interleukin (IL)-10 or IL-35) and pro-inflammatory B cells (secreting tumor necrosis factor α, LTα, IL-6, and granulocyte macrophage colony-stimulating factor). Better understanding of human cytokine-defined B cell responses is necessary in both health and diseases, such as MS. Investigation of their surface phenotype, distinct functions, and the mechanisms of regulation (both cell intrinsic and cell extrinsic) may help develop effective treatments that are more selective and safe. In this review, we focus on mechanisms by which cytokine-defined B cells contribute to the peripheral immune cascades that are thought to underlie MS relapses, and the impact of B cell-directed therapies on these mechanisms.
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University , Montreal, QC , Canada.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University , Montreal, QC , Canada.
authors.forename: Ayman
authors.initials: A
authors.lastname: Rezk
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University , Montreal, QC , Canada.
authors.forename: Luke M
authors.initials: LM
authors.lastname: Healy
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University , Montreal, QC , Canada.
authors.forename: Gillian
authors.initials: G
authors.lastname: Muirhead
authors.affiliation: Neuroimmunology Unit, Department of Neuroscience, Centre de Recherche du CHUM (CRCHUM), Université de Montreal , Montreal, QC , Canada.
authors.forename: Alexandre
authors.initials: A
authors.lastname: Prat
authors.affiliation: Department of Immunology, University of Toronto , Toronto, ON , Canada.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Gommerman
authors.affiliation: Neuroimmunology Unit, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada; Experimental Therapeutics Program, Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
authors.forename: Amit
authors.initials: A
authors.lastname: Bar-Or
keywords: B cell modulation; B-cell depletion; B-lymphocytes; cytokine-defined responses; immune modulation; multiple sclerosis