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However, the detailed mechanism of rFlaA:Betv1\u2010mediated immune modulation is not fully understood. In this study, we investigated the effect of rFlaA:Betv1 on na\u00efve murine B cells.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Immune modulating capacity of rFlaA:Betv1 was screened in IL\u201010 reporter mice. B cells were isolated from spleens of na\u00efve C57Bl\/6, TLR5<jats:sup>\u2212\/\u2212<\/jats:sup>, or MyD88<jats:sup>\u2212\/\u2212<\/jats:sup> mice, stimulated with rFlaA:Betv1 and controls, and monitored for the expression of the regulatory B cell markers CD1d, CD24, CD38, and surface IgM by flow cytometry. Secreted cytokines, antibodies, and reactivity of the induced antibodies were investigated by ELISA and intracellular flow cytometry. Suppressive capacity of rFlaA:Betv1\u2010stimulated B cells was tested in mDC:CD4<jats:sup>+<\/jats:sup> T cell:B cell triple cultures.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Upon in vivo application of rFlaA:Betv1 into IL\u201010\u2010GFP reporter mice, CD19<jats:sup>+<\/jats:sup> B cells were shown to produce anti\u2010inflammatory IL\u201010, suggesting B cells to contribute to the immune\u2010modulatory properties of rFlaA:Betv1. rFlaA:Betv1\u2010induced IL\u201010 secretion was confirmed in human B cells isolated from buffy coats. In vitro stimulation of na\u00efve murine B cells with rFlaA:Betv1 resulted in an mTOR\u2010 and MyD88\u2010dependent production of IL\u201010 and rFlaA:Betv1 induced Bet v 1\u2010reactive IgG production, which was not observed for IgA. rFlaA:Betv1\u2010stimulated B cells formed a CD19<jats:sup>+<\/jats:sup>CD24<jats:sup>+<\/jats:sup>CD1d<jats:sup>+<\/jats:sup>IgM<jats:sup>+<\/jats:sup>CD38<jats:sup>+<\/jats:sup> Breg subpopulation capable of suppressing Bet v 1\u2010induced TH2 cytokine secretion in vitro.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>rFlaA:Betv1 can act as a thymus\u2010independent B cell antigen, stimulating the mTOR\u2010 and MyD88\u2010dependent differentiation of B cells displaying a regulatory phenotype, IL\u201010 secretion, antigen\u2010binding antibody production, and a suppressive capacity in vitro.<\/jats:p><\/jats:sec>","DOI":"10.1111\/all.15542","type":"journal-article","created":{"date-parts":[[2022,10,5]],"date-time":"2022-10-05T06:09:16Z","timestamp":1664950156000},"page":"663-681","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Stimulation of na\u00efve B cells with a fusion protein consisting of <scp>FlaA<\/scp> and Bet v 1 induces regulatory B cells ex vivo"],"prefix":"10.1111","volume":"78","author":[{"given":"Alexandra","family":"Goretzki","sequence":"first","affiliation":[{"name":"Molecular Allergology Paul\u2010Ehrlich\u2010Institut  Langen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yen\u2010Ju","family":"Lin","sequence":"additional","affiliation":[{"name":"Molecular Allergology Paul\u2010Ehrlich\u2010Institut  Langen 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