What will B will B: identifying molecular determinants of diverse B-cell fate decisions through systems biology

Mitchell, Simon (2021) What will B will B: identifying molecular determinants of diverse B-cell fate decisions through systems biology. Frontiers in Cell and Developmental Biology, 8. a616592 1-8. ISSN 2296-634X

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Abstract

B-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.

Item Type: Article
Keywords: Systems Biology, B-cells, Computational Modelling, Heterogeneity, Cell Signalling, Cell Fate, NF-kB
Schools and Departments: Brighton and Sussex Medical School > Clinical and Experimental Medicine
SWORD Depositor: Mx Elements Account
Depositing User: Mx Elements Account
Date Deposited: 20 Jan 2021 07:45
Last Modified: 20 Jan 2021 08:01
URI: http://sro.sussex.ac.uk/id/eprint/96585

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