Enhanced protein synthesis is a defining requirement for neonatal B cell development
(2023) In Frontiers in Immunology- Abstract
- The LIN28B RNA binding protein exhibits an ontogenically restricted expression pattern and is a key molecular regulator of fetal and neonatal B lymphopoiesis. It enhances the positive selection of CD5+ immature B cells early in life through amplifying the CD19/PI3K/c-MYC pathway and is sufficient to reinitiate self-reactive B-1a cell output when ectopically expressed in the adult. In this study, interactome analysis in primary B cell precursors showed direct binding by LIN28B to numerous ribosomal protein transcripts, consistent with a regulatory role in cellular protein synthesis. Induction of LIN28B expression in the adult setting is sufficient to promote enhanced protein synthesis during the small Pre-B and immature B cell stages, but... (More)
- The LIN28B RNA binding protein exhibits an ontogenically restricted expression pattern and is a key molecular regulator of fetal and neonatal B lymphopoiesis. It enhances the positive selection of CD5+ immature B cells early in life through amplifying the CD19/PI3K/c-MYC pathway and is sufficient to reinitiate self-reactive B-1a cell output when ectopically expressed in the adult. In this study, interactome analysis in primary B cell precursors showed direct binding by LIN28B to numerous ribosomal protein transcripts, consistent with a regulatory role in cellular protein synthesis. Induction of LIN28B expression in the adult setting is sufficient to promote enhanced protein synthesis during the small Pre-B and immature B cell stages, but not during the Pro-B cell stage. This stage dependent effect was dictated by IL-7 mediated signaling, which masked the impact of LIN28B through an overpowering stimulation on the c-MYC/protein synthesis axis in Pro-B cells. Importantly, elevated protein synthesis was a distinguishing feature between neonatal and adult B cell development that was critically supported by endogenous Lin28b expression early in life. Finally, we used a ribosomal hypomorphic mouse model to demonstrate that subdued protein synthesis is specifically detrimental for neonatal B lymphopoiesis and the output of B-1a cells, without affecting B cell development in the adult. Taken together, we identify elevated protein synthesis as a defining requirement for early-life B cell development that critically depends on Lin28b. Our findings offer new mechanistic insights into the layered formation of the complex adult B cell repertoire. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/71216041-3458-485d-b744-30dcfbdbcf1e
- author
- Åkerstrand, Hugo LU ; Boldrin, Elena LU ; Montano, Giorgia LU ; Vanhee, Stijn LU ; Olsson, Karin LU ; Krausse, Niklas LU ; Vergani, Stefano LU ; Ciesla, Maciej LU ; Bellodi, Cristian LU and Yuan, Joan LU
- organization
- publishing date
- 2023
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Frontiers in Immunology
- publisher
- Frontiers Media S. A.
- external identifiers
-
- scopus:85159548016
- pmid:37138883
- ISSN
- 1664-3224
- DOI
- 10.3389/fimmu.2023.1130930
- language
- English
- LU publication?
- yes
- id
- 71216041-3458-485d-b744-30dcfbdbcf1e
- date added to LUP
- 2023-05-26 15:16:59
- date last changed
- 2024-04-05 19:58:35
@article{71216041-3458-485d-b744-30dcfbdbcf1e, abstract = {{The LIN28B RNA binding protein exhibits an ontogenically restricted expression pattern and is a key molecular regulator of fetal and neonatal B lymphopoiesis. It enhances the positive selection of CD5+ immature B cells early in life through amplifying the CD19/PI3K/c-MYC pathway and is sufficient to reinitiate self-reactive B-1a cell output when ectopically expressed in the adult. In this study, interactome analysis in primary B cell precursors showed direct binding by LIN28B to numerous ribosomal protein transcripts, consistent with a regulatory role in cellular protein synthesis. Induction of LIN28B expression in the adult setting is sufficient to promote enhanced protein synthesis during the small Pre-B and immature B cell stages, but not during the Pro-B cell stage. This stage dependent effect was dictated by IL-7 mediated signaling, which masked the impact of LIN28B through an overpowering stimulation on the c-MYC/protein synthesis axis in Pro-B cells. Importantly, elevated protein synthesis was a distinguishing feature between neonatal and adult B cell development that was critically supported by endogenous Lin28b expression early in life. Finally, we used a ribosomal hypomorphic mouse model to demonstrate that subdued protein synthesis is specifically detrimental for neonatal B lymphopoiesis and the output of B-1a cells, without affecting B cell development in the adult. Taken together, we identify elevated protein synthesis as a defining requirement for early-life B cell development that critically depends on Lin28b. Our findings offer new mechanistic insights into the layered formation of the complex adult B cell repertoire.}}, author = {{Åkerstrand, Hugo and Boldrin, Elena and Montano, Giorgia and Vanhee, Stijn and Olsson, Karin and Krausse, Niklas and Vergani, Stefano and Ciesla, Maciej and Bellodi, Cristian and Yuan, Joan}}, issn = {{1664-3224}}, language = {{eng}}, publisher = {{Frontiers Media S. A.}}, series = {{Frontiers in Immunology}}, title = {{Enhanced protein synthesis is a defining requirement for neonatal B cell development}}, url = {{http://dx.doi.org/10.3389/fimmu.2023.1130930}}, doi = {{10.3389/fimmu.2023.1130930}}, year = {{2023}}, }