Activation-Induced B Cell Fates Are Selected by Intracellular Stochastic Competition

被引:163
作者
Duffy, Ken R. [2 ]
Wellard, Cameron J. [1 ,3 ]
Markham, John F. [4 ]
Zhou, Jie H. S. [1 ,3 ]
Holmberg, Ross [1 ]
Hawkins, Edwin D. [5 ]
Hasbold, Jhagvaral [1 ,3 ]
Dowling, Mark R. [1 ,3 ]
Hodgkin, Philip D. [1 ,3 ]
机构
[1] Walter & Eliza Hall Inst Med Res, Melbourne, Vic 3052, Australia
[2] Natl Univ Ireland, Hamilton Inst, Maynooth, Kildare, Ireland
[3] Univ Melbourne, Dept Med Biol, Melbourne, Vic 3052, Australia
[4] Univ Melbourne, Natl Informat & Commun Technol ICT Australia, Victoria Res Lab, Melbourne, Vic 3010, Australia
[5] Peter MacCallum Canc Ctr, Immune Signalling Lab, Melbourne, Vic 3002, Australia
基金
澳大利亚国家健康与医学研究理事会; 英国医学研究理事会; 澳大利亚研究理事会; 爱尔兰科学基金会;
关键词
IMMUNE-RESPONSES; PLASMA-CELL; T-CELLS; LYMPHOCYTE DIVISION; POPULATION-DYNAMICS; DIFFERENTIATION; MECHANISM; MODEL; PROLIFERATION; VARIABILITY;
D O I
10.1126/science.1213230
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:338 / 341
页数:4
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