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Updated: Feb 28, 2026
In Vitro Differentiation Model of Human Normal Memory B Cells to Long-lived Plasma Cells
Published on: January 20, 2019
Integrated single cell multiomic profiling and functional validation reveal distinct cellular routes to human plasma
Colin A Fields1, James F Read1,2, Heather Coffman3
1Department of Immunobiology, University of Arizona, Tucson, AZ, 85724, USA.
B cells differentiate into distinct plasma cell subsets via unique routes. We identified a CD30+ intermediate, regulated by MEF2C, influencing B cell differentiation pathways.
Area of Science:
- Immunology
- Cell Biology
- Molecular Biology
Background:
- B cells undergo significant changes to become antibody-secreting plasma cells.
- Distinct plasma cell subsets and differentiation pathways exist.
Purpose of the Study:
- Identify distinct plasma cell subsets and differentiation routes.
- Investigate the role of CD30+ intermediates in B cell differentiation.
Main Methods:
- Single-cell RNA and ATAC sequencing of human B cells.
- Analysis of primary and in vitro differentiating B cells.
- Pharmacological inhibition experiments.
Main Results:
- Two distinct plasma cell subsets identified in tonsils based on CD44v9, CD38, CD31, and CD10 expression.
- A transient CD30+ intermediate was observed in both primary and in vitro settings.
- MEF2C promotes CD30+ intermediates, while BAFF and APRIL drive maturation to CD44v9+ plasma cells.
Conclusions:
- Human B cell differentiation pathways (germinal center-dependent and -independent) lead to distinct plasma cell outcomes.
- The CD30+ intermediate plays a crucial role in directing B cell differentiation routes.
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