B cell development is critically dependent on NFATc1 activity
dc.contributor.author | Giampaolo, S | |
dc.contributor.author | Wójcik, G | |
dc.contributor.author | Klein-Hessling, S | |
dc.contributor.author | Serfling, E | |
dc.contributor.author | Patra, AK | |
dc.date.accessioned | 2019-01-21T10:34:43Z | |
dc.date.issued | 2019-05 | |
dc.identifier.issn | 2042-0226 | |
dc.identifier.issn | 2042-0226 | |
dc.identifier.uri | http://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.extent | 508-520 | |
dc.format.medium | Print-Electronic | |
dc.language | en | |
dc.language.iso | en | |
dc.publisher | Springer Nature [academic journals on nature.com] | |
dc.subject | Differentiation | |
dc.subject | EBF1 | |
dc.subject | NFATc1 | |
dc.subject | Pro-B | |
dc.subject | Pre-B | |
dc.title | B cell development is critically dependent on NFATc1 activity | |
dc.type | journal-article | |
dc.type | Journal Article | |
dc.type | Research Support, Non-U.S. Gov't | |
plymouth.author-url | https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000464963900010&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=11bb513d99f797142bcfeffcc58ea008 | |
plymouth.issue | 5 | |
plymouth.volume | 16 | |
plymouth.publication-status | Published | |
plymouth.journal | Cellular and Molecular Immunology | |
dc.identifier.doi | 10.1038/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.place | China | |
dcterms.dateAccepted | 2018-05-23 | |
dc.rights.embargodate | 2019-3-20 | |
dc.identifier.eissn | 2042-0226 | |
dc.rights.embargoperiod | Not known | |
rioxxterms.versionofrecord | 10.1038/s41423-018-0052-9 | |
rioxxterms.licenseref.uri | http://www.rioxx.net/licenses/all-rights-reserved | |
rioxxterms.type | Journal Article/Review |