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In MS<\/jats:styled-content> and other autoimmune diseases decreased frequency and functionality of Breg cells correlate with disease activity and the percentage of IL<\/jats:styled-content>\u201010\u2010producing Breg cells decreases during relapse and normalizes in remission. Optic neuritis (ON<\/jats:styled-content>) is a common first clinical manifestation of MS<\/jats:styled-content> and IL<\/jats:styled-content>\u201010\u2010producing Breg cells may be crucial in the transition from ON<\/jats:styled-content> to MS<\/jats:styled-content>, we therefore investigate the frequency and function of Breg cells in ON<\/jats:styled-content> as a clinical model of early demyelinating disease. B cells were purified from 27 patients with ON<\/jats:styled-content> sampled close to symptom onset (median 23\u00a0days, range 7\u201341\u00a0days) and 13 healthy controls. The B cells were stimulated and cultured for 48\u00a0hr with CD<\/jats:styled-content>40 ligand and CpG before measurement of intracellular IL<\/jats:styled-content>\u201010 and the surface markers CD<\/jats:styled-content>19, CD<\/jats:styled-content>1d, CD<\/jats:styled-content>5, CD<\/jats:styled-content>24, CD<\/jats:styled-content>38 and CD<\/jats:styled-content>27 by flow cytometry. The frequency of B\u2010cell subsets was analysed in peripheral blood and cerebral spinal fluid (CSF<\/jats:styled-content>) of patients. Sixty\u2010five per\u00a0cent of the IL<\/jats:styled-content>\u201010\u2010producing Breg cells co\u2010expressed CD<\/jats:styled-content>24 and CD<\/jats:styled-content>38, and only 14% were CD<\/jats:styled-content>24high<\/jats:sup>\u00a0CD<\/jats:styled-content>27+<\/jats:sup>, suggesting that the naive B cells are the primary source of IL<\/jats:styled-content>\u201010 in the B\u2010cell culture, followed by memory cells in both healthy controls and patients. The frequency of naive CD<\/jats:styled-content>19+<\/jats:sup>\u00a0CD<\/jats:styled-content>24+<\/jats:sup>\u00a0CD<\/jats:styled-content>38+<\/jats:sup> Breg cells was higher in patients with ON<\/jats:styled-content> compared with controls. The ability of Breg cells to produce IL<\/jats:styled-content>\u201010 was at normal levels in both ON<\/jats:styled-content> patients with high risk and those with low risk of progression to MS<\/jats:styled-content>. We found no correlation between Breg cell function and the presence of brain white matter lesions by magnetic resonance imaging or CSF<\/jats:styled-content> oligoclonal bands indicative of ON<\/jats:styled-content> patients carrying a higher risk of conversion to MS<\/jats:styled-content>. The frequencies of IL<\/jats:styled-content>\u201010\u2010producing B cells did not correlate with the conversion to MS<\/jats:styled-content> at 2\u2010year follow up. Interleukin\u201010 was primarily produced by naive and memory B cells. The frequency of IL<\/jats:styled-content>\u201010\u2010secreting B cells did not correlate with risk factors of MS<\/jats:styled-content>. Breg cell function at clinical onset of ON<\/jats:styled-content> is not a determining factor for conversion to MS<\/jats:styled-content>.<\/jats:p><\/jats:sec>","DOI":"10.1111\/imm.13024","type":"journal-article","created":{"date-parts":[[2018,11,19]],"date-time":"2018-11-19T15:38:13Z","timestamp":1542641893000},"page":"259-269","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Frequency and immunophenotype of IL<\/scp>10\u2010producing regulatory B cells in optic neuritis"],"prefix":"10.1111","volume":"156","author":[{"given":"Sara","family":"Lundqvist","sequence":"first","affiliation":[{"name":"MS Clinic Department of Neurology Rigshospitalet Glostrup University of Copenhagen Glostrup Denmark"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Signe","family":"Modvig","sequence":"additional","affiliation":[{"name":"MS Clinic Department of Neurology Rigshospitalet Glostrup University of Copenhagen 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