title: New regulatory CD19(+)CD25(+) B-cell subset in clinically isolated syndrome and multiple sclerosis relapse. Changes after glucocorticoids.
abstract: In multiple sclerosis (MS), the immune damage to the central nervous system results from the net balance between self-reactive and immunoregulatory cells, among other factors. We identified novel perforin-expressing regulatory B-cells (BReg) in patients with clinically isolated syndrome, significantly enriched within the cerebrospinal fluid when compared to peripheral blood, of memory B cell phenotype (CD19(+)CD25(+), CD19(+)CD25(+)FoxP3(+) and CD19(+)FoxP3(+), p=0.007, p=0.06 and p=0.03, respectively). These BReg subsets were also higher in relapsing-remitting MS during relapse symptoms than in non-clinically active MS patients. Suppressive effects by CD19(+)CD25(+hi) BReg on CD4(+) T cell proliferation seem to be mediated at least in part by perforin/granzyme pathway. To our knowledge, this is the first report that shows cytolytic perforin/granzyme granule storage in B cells; the interesting point is its involvement on BReg cell immunosuppressive mechanisms, similarly to that in TReg cells. Our data may extend the understanding of pathophysiological processes in MS immunoregulation.
authors.affiliation: Department of Neurology, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo 46, 28007 Madrid, Spain. Electronic address: claradeandres@hotmail.com.
authors.forename: Clara
authors.initials: C
authors.lastname: de Andrés
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Tejera-Alhambra
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Alonso
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Lara
authors.initials: L
authors.lastname: Valor
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Roseta
authors.initials: R
authors.lastname: Teijeiro
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Rocío
authors.initials: R
authors.lastname: Ramos-Medina
authors.affiliation: Department of Neurology, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo 46, 28007 Madrid, Spain.
authors.forename: Dolores
authors.initials: D
authors.lastname: Mateos
authors.affiliation: INSERM U932, Institut Curie, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Faure
authors.affiliation: Department of Immunology, Hospital General Universitario Gregorio Marañón, c/Doctor Esquerdo 46, 28007 Madrid, Spain; Department of Clinical Immunology, Hospital Clínico San Carlos, Madrid, Spain.
authors.forename: Silvia
authors.initials: S
authors.lastname: Sánchez-Ramón
mesh_terms: D000328:Adult; D018941:Antigens, CD19 / Q000276:immunology; D060151:B-Lymphocytes, Regulatory / Q000276:immunology* / Q000378:metabolism; D003430:Cross-Sectional Studies; D003711:Demyelinating Diseases / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology*; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D053804:Granzymes / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D006801:Humans; D053645:Interleukin-2 Receptor alpha Subunit / Q000276:immunology; D008297:Male; D008775:Methylprednisolone / Q000627:therapeutic use*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy* / Q000276:immunology* / Q000378:metabolism; D054353:Perforin / Q000032:analysis / Q000276:immunology / Q000378:metabolism; D012008:Recurrence; D050378:T-Lymphocytes, Regulatory / Q000276:immunology; D055815:Young Adult
chemical_list: D018941:Antigens, CD19; D005938:Glucocorticoids; C508017:IL2RA protein, human; D053645:Interleukin-2 Receptor alpha Subunit; D054353:Perforin; D053804:Granzymes; D008775:Methylprednisolone
keywords: Multiple sclerosis, cerebrospinal fluid; Perforin expression, methylprednisolone; Regulatory B-lymphocytes