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dc.contributor.authorGiampaolo, S
dc.contributor.authorWójcik, G
dc.contributor.authorKlein-Hessling, S
dc.contributor.authorSerfling, E
dc.contributor.authorPatra, AK
dc.date.accessioned2019-01-21T10:34:43Z
dc.date.issued2019-05
dc.identifier.issn2042-0226
dc.identifier.issn2042-0226
dc.identifier.urihttp://hdl.handle.net/10026.1/13175
dc.description.abstract

B cell development in bone marrow is a precisely regulated complex process. Through successive stages of differentiation, which are regulated by a multitude of signaling pathways and an array of lineage-specific transcription factors, the common lymphoid progenitors ultimately give rise to mature B cells. Similar to early thymocyte development in the thymus, early B cell development in bone marrow is critically dependent on IL-7 signaling. During this IL-7-dependent stage of differentiation, several transcription factors, such as E2A, EBF1, and Pax5, among others, play indispensable roles in B lineage specification and maintenance. Although recent studies have implicated several other transcription factors in B cell development, the role of NFATc1 in early B cell developmental stages is not known. Here, using multiple gene-manipulated mouse models and applying various experimental methods, we show that NFATc1 activity is vital for early B cell differentiation. Lack of NFATc1 activity in pro-B cells suppresses EBF1 expression, impairs immunoglobulin gene rearrangement, and thereby preBCR formation, resulting in defective B cell development. Overall, deficiency in NFATc1 activity arrested the pro-B cell transition to the pre-B cell stage, leading to severe B cell lymphopenia. Our findings suggest that, along with other transcription factors, NFATc1 is a critical component of the signaling mechanism that facilitates early B cell differentiation.

dc.format.extent508-520
dc.format.mediumPrint-Electronic
dc.languageen
dc.language.isoen
dc.publisherSpringer Nature [academic journals on nature.com]
dc.subjectDifferentiation
dc.subjectEBF1
dc.subjectNFATc1
dc.subjectPro-B
dc.subjectPre-B
dc.titleB cell development is critically dependent on NFATc1 activity
dc.typejournal-article
dc.typeJournal Article
dc.typeResearch Support, Non-U.S. Gov't
plymouth.author-urlhttps://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000464963900010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008
plymouth.issue5
plymouth.volume16
plymouth.publication-statusPublished
plymouth.journalCellular and Molecular Immunology
dc.identifier.doi10.1038/s41423-018-0052-9
plymouth.organisational-group/Plymouth
plymouth.organisational-group/Plymouth/Faculty of Health
plymouth.organisational-group/Plymouth/Faculty of Health/Peninsula Medical School
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA
plymouth.organisational-group/Plymouth/REF 2021 Researchers by UoA/UoA01 Clinical Medicine
plymouth.organisational-group/Plymouth/Users by role
plymouth.organisational-group/Plymouth/Users by role/Academics
dc.publisher.placeChina
dcterms.dateAccepted2018-05-23
dc.rights.embargodate2019-3-20
dc.identifier.eissn2042-0226
dc.rights.embargoperiodNot known
rioxxterms.versionofrecord10.1038/s41423-018-0052-9
rioxxterms.licenseref.urihttp://www.rioxx.net/licenses/all-rights-reserved
rioxxterms.typeJournal Article/Review


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