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Please use this identifier to cite or link to this item: http://hdl.handle.net/1942/23234

Title: Age-Associated B Cells with Proinflammatory Characteristics Are Expanded in a Proportion of Multiple Sclerosis Patients
Authors: Claes, Nele
Fraussen, Judith
Vanheusden, Marjan
Hellings, Niels
Stinissen, Piet
Van Wijmeersch, Bart
Hupperts, Raymond
Somers, Veerle
Issue Date: 2016
Citation: JOURNAL OF IMMUNOLOGY, 197(12), p. 4576-4583
Abstract: Immune aging occurs in the elderly and in autoimmune diseases. Recently, IgD(-) CD27(-) (double negative, DN) and CD21(-) CD11c(+) (CD21(low)) B cells were described as age- associated B cells with proinflammatory characteristics. This study investigated the prevalence and functional characteristics of DN and CD21(low) B cells in multiple sclerosis (MS) patients. Using flow cytometry, we demonstrated a higher proportion of MS patients younger than 60 y with peripheral expansions of DN (8/41) and CD21(low) (9/41) B cells compared with age- matched healthy donors (1/33 and 2/33, respectively), which indicates an increase in age- associated B cells in MS patients. The majority of DN B cells had an IgG(+) memory phenotype, whereas CD21(low) B cells consisted of a mixed population of CD27(-) naive, CD27(+) memory, IgG(+), and IgM(+) cells. DN B cells showed similar (MS patients) or increased (healthy donors) MHC-II expression as class- switched memory B cells and intermediate costimulatory molecule expression between naive and class- switched memory B cells, indicating their potential to induce (proinflammatory) T cell responses. Further, DN B cells produced proinflammatory and cytotoxic cytokines following ex vivo stimulation. Increased frequencies of DN and CD21(low) B cells were found in the cerebrospinal fluid of MS patients compared with paired peripheral blood. In conclusion, a proportion of MS patients showed increased peripheral expansions of age- associated B cells. DN and CD21(low) B cell frequencies were further increased in MS cerebrospinal fluid. These cells could contribute to inflammation by induction of T cell responses and the production of proinflammatory cytokines.
Notes: [Claes, Nele; Fraussen, Judith; Vanheusden, Marjan; Hellings, Niels; Stinissen, Piet; Van Wijmeersch, Bart; Somers, Veerle] Hasselt Univ, Biomed Res Inst, Martelarenlaan 42, B-3500 Hasselt, Belgium. [Claes, Nele; Fraussen, Judith; Vanheusden, Marjan; Hellings, Niels; Stinissen, Piet; Van Wijmeersch, Bart; Somers, Veerle] Transnat Univ Limburg, Sch Life Sci, B-3590 Diepenbeek, Belgium. [Van Wijmeersch, Bart] Rehabil & MS Ctr, B-3900 Overpelt, Belgium. [Hupperts, Raymond] Maastricht Univ, Sch Mental Hlth & Neurosci, Dept Neurosci, NL-6229 ER Maastricht, Netherlands. [Hupperts, Raymond] Zuyderland Med Ctr, Acad MS Ctr Limburg, Dept Neurol, NL-6162 BG Sittard, Netherlands.
URI: http://hdl.handle.net/1942/23234
DOI: 10.4049/jimmunol.1502448
ISI #: 000389635900009
ISSN: 0022-1767
Category: A1
Type: Journal Contribution
Appears in Collections: Research publications

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