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Science 335 (6066): 338-341

Copyright © 2012 by the American Association for the Advancement of Science

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

Ken R. Duffy,1 Cameron J. Wellard,2,3 John F. Markham,4 Jie H. S. Zhou,2,3 Ross Holmberg,2 Edwin D. Hawkins,5 Jhagvaral Hasbold,2,3 Mark R. Dowling,2,3,* Philip D. Hodgkin2,3,*,{dagger}

Abstract: 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.

1 Hamilton Institute, National University of Ireland, Maynooth, Ireland.
2 Walter and Eliza Hall Institute of Medical Research, Parkville, Melbourne, Victoria 3052, Australia.
3 Department of Medical Biology, University of Melbourne, Melbourne, Victoria 3052, Australia.
4 Victoria Research Laboratory, National Information and Communications Technology (ICT) Australia, University of Melbourne, Melbourne, Victoria 3010, Australia.
5 Immune Signalling Laboratory, Peter MacCallum Cancer Centre, Melbourne, Victoria 3002, Australia.

* These authors contributed equally to this work.

{dagger} To whom correspondence should be addressed. E-mail: hodgkin{at}wehi.edu.au


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