fcell-08-616592.pdf (1.41 MB)
What will B will B: identifying molecular determinants of diverse B-cell fate decisions through systems biology
Version 2 2023-06-12, 09:41
Version 1 2023-06-09, 22:49
journal contribution
posted on 2023-06-12, 09:41 authored by Simon MitchellSimon MitchellB-cells are the poster child for cellular diversity and heterogeneity. The diverse repertoire of B lymphocytes, each expressing unique antigen receptors, provides broad protection against pathogens. However, B-cell diversity goes beyond unique antigen receptors. Side-stepping B-cell receptor (BCR) diversity through BCR-independent stimuli or engineered organisms with monoclonal BCRs still results in seemingly identical B-cells reaching a wide variety of fates in response to the same challenge. Identifying to what extent the molecular state of a B-cell determines its fate is key to gaining a predictive understanding of B-cells and consequently the ability to control them with targeted therapies. Signals received by B-cells through transmembrane receptors converge on intracellular molecular signaling networks, which control whether each B-cell divides, dies, or differentiates into a number of antibody-secreting distinct B-cell subtypes. The signaling networks that interpret these signals are well known to be susceptible to molecular variability and noise, providing a potential source of diversity in cell fate decisions. Iterative mathematical modeling and experimental studies have provided quantitative insight into how B-cells achieve distinct fates in response to pathogenic stimuli. Here, we review how systems biology modeling of B-cells, and the molecular signaling networks controlling their fates, is revealing the key determinants of cell-to-cell variability in B-cell destiny.
Funding
Diffused large B-cell lymphoma stratification and therapeutic targeting through systems biology; G3210; UK RESEARCH AND INNOVATION; UKRI Future Lea
A Systems Biology Approach to Tailoring Therapy for Diffuse Large B-Cell Lymphoma; G3110; LEUKAEMIA UK; 2020/JGF/003
Diffuse Large B-cell lymphoma (DLBCL); G2963; BEAT:CANCER; BEATCANCER
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Publication status
- Published
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- Published version
Journal
Frontiers in Cell and Developmental BiologyISSN
2296-634XPublisher
Frontiers MediaExternal DOI
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8Page range
1-8Article number
a616592Department affiliated with
- Clinical and Experimental Medicine Publications
Full text available
- Yes
Peer reviewed?
- Yes
Legacy Posted Date
2021-01-20First Open Access (FOA) Date
2021-01-20First Compliant Deposit (FCD) Date
2021-01-19Usage metrics
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