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Immunol."],"abstract":"<jats:p>\n                    Double negative (DN) (CD19\n                    <jats:sup>+<\/jats:sup>\n                    CD20\n                    <jats:sup>low<\/jats:sup>\n                    CD27\n                    <jats:sup>-<\/jats:sup>\n                    IgD\n                    <jats:sup>-<\/jats:sup>\n                    ) B cells are expanded in patients with autoimmune and infectious diseases; however their role in the humoral immune response remains unclear. Using systematic flow cytometric analyses of peripheral blood B cell subsets, we observed an inflated DN B cell population in patients with variety of active inflammatory conditions: myasthenia gravis, Guillain-Barr\u00e9 syndrome, neuromyelitis optica spectrum disorder, meningitis\/encephalitis, and rheumatic disorders. Furthermore, we were able to induce DN B cells in healthy subjects following vaccination against influenza and tick borne encephalitis virus. Transcriptome analysis revealed a gene expression profile in DN B cells that clustered with na\u00efve B cells, memory B cells, and plasmablasts. Immunoglobulin VH transcriptome sequencing and analysis of recombinant antibodies revealed clonal expansion of DN B cells that were targeted against the vaccine antigen. Our study suggests that DN B cells are expanded in multiple inflammatory neurologic diseases and represent an inducible B cell population that responds to antigenic stimulation, possibly through an extra-follicular maturation pathway.\n                  <\/jats:p>","DOI":"10.3389\/fimmu.2020.606338","type":"journal-article","created":{"date-parts":[[2020,12,18]],"date-time":"2020-12-18T00:03:02Z","timestamp":1608249782000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":58,"title":["Specific Induction of Double Negative B Cells During Protective and Pathogenic Immune Responses"],"prefix":"10.3389","volume":"11","author":[{"given":"Christoph","family":"Ruschil","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gisela","family":"Gabernet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gildas","family":"Lepennetier","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simon","family":"Heumos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miriam","family":"Kaminski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zsuzsanna","family":"Hracsko","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Irmler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Johannes","family":"Beckers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Ziemann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sven","family":"Nahnsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gregory P.","family":"Owens","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernhard","family":"Hemmer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus C.","family":"Kowarik","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2019.02458","article-title":"Challenges and Opportunities for Consistent Classification of Human B Cell and Plasma Cell Populations","volume":"10","author":"Sanz","year":"2019","journal-title":"Front Immunol"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1038\/ni.3175","article-title":"Diversity, cellular origin and autoreactivity of antibody-secreting cell expansions in acute Systemic Lupus Erythematosus","volume":"16","author":"Tipton","year":"2015","journal-title":"Nat Immunol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.immuni.2018.08.015","article-title":"Distinct effector B cells induced by unregulated toll-like receptor 7 contribute to pathogenic responses in systemic lupus erythematosus","volume":"49","author":"Jenks","year":"2018","journal-title":"Immunity"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1502448","article-title":"Age-Associated B Cells with Proinflammatory Characteristics Are Expanded in a Proportion of Multiple Sclerosis Patients","volume":"197","author":"Claes","year":"2016","journal-title":"J Immunol"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.mad.2009.08.003","article-title":"Caruso C. 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