Medical Biology - Research Publications
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ItemIntracellular competition for fates in the immune system(ELSEVIER SCIENCE LONDON, 2012-09)During an adaptive immune response, lymphocytes proliferate for five to 20 generations, differentiating to take on effector functions, before cessation and cell death become dominant. Recent experimental methodologies enable direct observation of individual lymphocytes and the times at which they adopt fates. Data from these experiments reveal diversity in fate selection, heterogeneity and involved correlation structures in times to fate, as well as considerable familial correlations. Despite the significant complexity, these data are consistent with the simple hypothesis that each cell possesses autonomous processes, subject to temporal competition, leading to each fate. This article addresses the evidence for this hypothesis, its hallmarks, and, should it be an appropriate description of a cell system, its ramifications for manipulation.
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ItemActivation-Induced B Cell Fates Are Selected by Intracellular Stochastic Competition(AMER ASSOC ADVANCEMENT SCIENCE, 2012-01-20)In response to stimulation, B lymphocytes pursue a large number of distinct fates important for immune regulation. Whether each cell's fate is determined by external direction, internal stochastic processes, or directed asymmetric division is unknown. Measurement of times to isotype switch, to develop into a plasmablast, and to divide or to die for thousands of cells indicated that each fate is pursued autonomously and stochastically. As a consequence of competition between these processes, censorship of alternative outcomes predicts intricate correlations that are observed in the data. Stochastic competition can explain how the allocation of a proportion of B cells to each cell fate is achieved. The B cell may exemplify how other complex cell differentiation systems are controlled.