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Updated: May 28, 2025
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In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
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Distinct plasmablast developmental intermediates produce graded expression of IgM secretory transcripts
Evelyn P Sievert1, Marissa C Franke1, Kayla B Thomas1
1Department of Anatomy, Physiology, and Cell Biology, University of California at Davis, Davis, CA, USA.
Cell Reports
|February 9, 2025
Summary
Plasma cells (PCs) secrete vast amounts of antibodies by altering immunoglobulin M (IgM) processing. This study reveals how transcription factors IRF4 and Blimp-1 control IgM switching and secretory pathway changes during PC differentiation.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- Plasma cells (PCs) secrete immunoglobulins at high rates, requiring significant cellular adaptations.
- PC differentiation involves complex transcriptional and post-transcriptional regulation to meet secretory demands.
Purpose of the Study:
- To investigate the post-transcriptional regulation of immunoglobulin M (IgM) during plasma cell differentiation.
- To elucidate the roles of IRF4 and Blimp-1 in controlling IgM polyadenylation site (PAS) usage and secretory pathway remodeling.
Main Methods:
- Development of a dual-fluorescent protein reporter mouse model to track IgM membrane-bound (μM-PAS) and secretory (μS-PAS) forms.
- Analysis of graded μS-PAS usage and Blimp-1 expression during PC differentiation.
- Examination of distinct developmental intermediates and their endoplasmic reticulum features.
Main Results:
- Observed graded usage of μS-PAS during plasma cell differentiation.
- Demonstrated hierarchical function of IRF4 and Blimp-1 in increasing IgM abundance and μS-PAS usage.
- Identified distinct cell populations with graded μS and Blimp-1 expression arising from different developmental intermediates.
Conclusions:
- IRF4 and Blimp-1 orchestrate the switch from membrane-bound to secretory IgM.
- Distinct cell trajectories and μS-PAS fate during differentiation impact secretory pathway adaptation.
- Findings provide insights into the cellular mechanisms supporting high-rate antibody secretion.
Keywords:
B cell differentiationCP: ImmunologyIgMalternative polyadenylationantibodyplasma cellsecretionMore Related Videos
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