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Janus kinase inhibitors (JAKi), which target downstream signaling of cytokine receptors, are potent rheumatic disease\u2010modifying drugs. However, besides reducing inflammation, JAKi may impact the adaptive immune system. In this study, we examined the effects of JAKi on B\u2010cell function using in vitro cultures and multiparameter flow cytometry. The results show a JAKi\u2010mediated reduction in plasma cell differentiation, primarily by inhibition of memory B\u2010cell stimulation and proliferation. JAKi exposure resulted in stalling R848, IL\u20102, and IL\u201021 stimulated B cells in an intermediate activated state with elevated na\u00efve cells displaying increased expression of CXCR5, CD71, CD22, and CD20. In addition, the data demonstrate a moderate JAKi\u2010mediated reduction of B cell TNF and IL\u20108 cytokine expression following stimulation. Importantly, the efficacy varied greatly between drugs; tofacitinib and upadacitinib (pan JAKi; JAK1i) exhibited the strongest impact, while baricitinib (JAK1\/JAK2i) showed donor\u2010dependent variation, and filgotinib (JAK1i) had no effect. All JAKi, except filgotinib, inhibited IL\u20102 or IL\u201021\u2010induced STAT3 phosphorylation. Still, filgotinib demonstrated similar inhibition of phospho\u2010STAT5 as other JAKi following IL\u201021. These findings underscore the therapeutic impact of JAKi through the modulation of B\u2010cell functions.<\/jats:p>","DOI":"10.1002\/eji.202451437","type":"journal-article","created":{"date-parts":[[2025,3,18]],"date-time":"2025-03-18T02:26:26Z","timestamp":1742264786000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["JAK Inhibitors and B Cell Function: A Comparative Study of Their Impact on Plasma Cell Differentiation, Cytokine Production, and Na\u00efve B Cell Activation"],"prefix":"10.1002","volume":"55","author":[{"given":"Wenqi","family":"Huang","sequence":"first","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charlotte","family":"de Vries","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2658-0002","authenticated-orcid":false,"given":"Ravi Kumar","family":"Sharma","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"},{"name":"Department of Clinical Immunology and Rheumatology All India Institute of Medical Sciences  Bilaspur India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kittikorn","family":"Wangriatisak","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katerina","family":"Chatzidionysiou","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9251-8082","authenticated-orcid":false,"given":"Vivianne","family":"Malmstr\u00f6m","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9111-5537","authenticated-orcid":false,"given":"Caroline","family":"Gr\u00f6nwall","sequence":"additional","affiliation":[{"name":"Division of Rheumatology, Department of Medicine Solna, Karolinska Institutet, Center for Molecular Medicine Karolinska University Hospital  Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/eji.202149675"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/ard-2022-223365"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41584-021-00726-8"},{"key":"e_1_2_10_5_1","first-page":"183","article-title":"Cardiovascular Safety, Cancer and Jak\u2010inhibitors: Differences to be Highlighted","author":"Benucci M.","year":"2022","journal-title":"Pharmacological Research"},{"key":"e_1_2_10_6_1","first-page":"201","article-title":"Evaluation of VTE, MACE, and Serious Infections among Patients With RA Treated With Baricitinib Compared to TNFi: A Multi\u2010Database Study of Patients in Routine Care Using Disease Registries and Claims Databases","volume":"10","author":"Salinas C. 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