RNA binding proteins control the G <sub>2</sub> -M checkpoint of the germinal center B cell

The germinal center (GC) reaction drives the production of high-affinity antibodies by iterative cycles of B cell somatic hypermutation, selection, and proliferation. How GC B cells undergo rapid cell division while maintaining genome stability is poorly understood. Here, we show that the RNA binding proteins ZFP36L1 and ZFP36L2 act downstream of antigen sensing and protect GC B cells from replication stress by controlling a cell cycle-related posttranscriptional regulon. They safeguard the successful completion of mitosis by balancing CDK1 and p21-mediated regulation of cell-cycle progression. In their absence, GC B cells are prone to arrest in the G<sub>2</sub>-M phase and die by apoptosis, resulting in curtailed GC responses. DNA replication forks stalled at active replication initiation zones, causing replication stress and increased activity of the ATR-CHK1 DNA damage response. Thus, RNA binding proteins guide posttranscriptional gene regulation and maintain a functional G<sub>2</sub>-M checkpoint in GC B cells.

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Publication Details

Journal
Science Immunology
Published
2025-10-31
DOI
https://doi.org/10.1126/sciimmunol.adu3718
Citations
2
Primary Topic
T-cell and B-cell Immunology
Type
article
Field-Weighted Citation Impact
1.59
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article

RNA binding proteins control the G 2 -M checkpoint of the germinal center B cell

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2 citations
Science Immunology
T-cell and B-cell Immunology
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article

RNA binding proteins control the G 2 -M checkpoint of the germinal center B cell

Michael Screen, Davide Maria Vespasiani, Jonathan M. Houseley, Martin Turner, Louise S. Matheson, Fiamma Salerno, Alex Whale, Michelle A. Linterman, Daniel J. Hodson, Melanie Stammers, Twm J. Mitchell, Hamish W. King, William S. Foster, Sarah E. Bell
article en
2 citations

Abstract

The germinal center (GC) reaction drives the production of high-affinity antibodies by iterative cycles of B cell somatic hypermutation, selection, and proliferation. How GC B cells undergo rapid cell division while maintaining genome stability is poorly understood. Here, we show that the RNA binding proteins ZFP36L1 and ZFP36L2 act downstream of antigen sensing and protect GC B cells from replication stress by controlling a cell cycle-related posttranscriptional regulon. They safeguard the successful completion of mitosis by balancing CDK1 and p21-mediated regulation of cell-cycle progression. In their absence, GC B cells are prone to arrest in the G<sub>2</sub>-M phase and die by apoptosis, resulting in curtailed GC responses. DNA replication forks stalled at active replication initiation zones, causing replication stress and increased activity of the ATR-CHK1 DNA damage response. Thus, RNA binding proteins guide posttranscriptional gene regulation and maintain a functional G<sub>2</sub>-M checkpoint in GC B cells.

Science ImmunologyVol. 10(112)
Babraham Institute (GB), Walter and Eliza Hall Institute of Medical Research (AU), Malaghan Institute of Medical Research (NZ), Wellcome/MRC Cambridge Stem Cell Institute (GB), University of Cambridge (GB), Leiden University Medical Center (NL)
Openalex Percentile: Top 14%
T-cell and B-cell Immunology
1.59
DOISourceOpenAlex
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