title: B Lymphocytes in Multiple Sclerosis: Bregs and BTLA/CD272 Expressing-CD19+ Lymphocytes Modulate Disease Severity.
abstract: B lymphocytes contribute to the pathogenesis of Multiple Sclerosis (MS) by secreting antibodies and producing cytokines. This latter function was analyzed in myelin olygodendrocyte protein (MOG)-stimulated CD19+ B lymphocytes of 71 MS patients with different disease phenotypes and 40 age-and sex-matched healthy controls (HC). Results showed that: 1) CD19+/TNFα+, CD19+/IL-12+ and CD19+/IFNγ+ lymphocytes are significantly increased in primary progressive (PP) compared to secondary progressive (SP), relapsing-remitting (RR), benign (BE) MS and HC; 2) CD19+/IL-6+ lymphocytes are significantly increased in PP, SP and RR compared to BEMS and HC; and 3) CD19+/IL-13+, CD19+/IL-10+, and CD19+/IL-10+/TGFβ+ (Bregs) B lymphocytes are reduced overall in MS patients compared to HC. B cells expressing BTLA, a receptor whose binding to HVEM inhibits TcR-initiated cytokine production, as well as CD19+/BTLA+/IL-10+ cells were also significantly overall reduced in MS patients compared to HC. Analyses performed in RRMS showed that fingolimod-induced disease remission is associated with a significant increase in Bregs, CD19+/BTLA+, and CD19+/BTLA+/IL-10+ B lymphocytes. B lymphocytes participate to the pathogenesis of MS via the secretion of functionally-diverse cytokines that might play a role in determining disease phenotypes. The impairment of Bregs and CD19+/BTLA+ cells, in particular, could play an important pathogenic role in MS.
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Federica
authors.initials: F
authors.lastname: Piancone
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Marina
authors.initials: M
authors.lastname: Saresella
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Ivana
authors.initials: I
authors.lastname: Marventano
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: La Rosa
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Martina
authors.initials: M
authors.lastname: Zoppis
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Simone
authors.initials: S
authors.lastname: Agostini
authors.affiliation: Institute of chemistry of molecular recognition, National Research Council, Milan, Italy.
authors.forename: Renato
authors.initials: R
authors.lastname: Longhi
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Domenico
authors.initials: D
authors.lastname: Caputo
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Laura
authors.initials: L
authors.lastname: Mendozzi
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Rovaris
authors.affiliation: Don C. Gnocchi Foundation, IRCCS, Piazza Morandi, 3, 20121 Milan, Italy.|Department of Physiopathology and Transplants, University of Milano, 20100 Milan, Italy.
authors.forename: Mario
authors.initials: M
authors.lastname: Clerici
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000276:immunology* / Q000378:metabolism; D060151:B-Lymphocytes, Regulatory / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D002478:Cells, Cultured; D005260:Female; D000068876:Fingolimod Hydrochloride / Q000627:therapeutic use; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D007371:Interferon-gamma / Q000276:immunology / Q000378:metabolism; D016753:Interleukin-10 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D018664:Interleukin-12 / Q000276:immunology / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D011971:Receptors, Immunologic / Q000276:immunology* / Q000378:metabolism; D012720:Severity of Illness Index; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; C482586:BTLA protein, human; D007166:Immunosuppressive Agents; D011971:Receptors, Immunologic; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12; D007371:Interferon-gamma; D000068876:Fingolimod Hydrochloride