B cell development is critically dependent on NFATc1 activity
Please always quote using this URN: urn:nbn:de:bvb:20-opus-233006
- 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, andB 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.…
Author: | Sabrina Giampaolo, Gabriela Wójcik, Stefan Klein-Hessling, Edgar Serfling, Amiya K. Patra |
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URN: | urn:nbn:de:bvb:20-opus-233006 |
Document Type: | Journal article |
Faculties: | Medizinische Fakultät / Pathologisches Institut |
Medizinische Fakultät / Comprehensive Cancer Center Mainfranken | |
Language: | English |
Parent Title (English): | Cellular & Molecular Immunology |
Year of Completion: | 2019 |
Volume: | 16 |
Pagenumber: | 508-520 |
Source: | Cellular & Molecular Immunology (2019) 16:508–520. https://doi.org/10.1038/s41423-018-0052-9 |
DOI: | https://doi.org/10.1038/s41423-018-0052-9 |
Dewey Decimal Classification: | 6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit |
Tag: | EBF1; NFATc1; differentiation; pre-B; pro-B |
Release Date: | 2024/06/27 |
Licence (German): | CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International |