Stochastically Timed Competition Between Division and Differentiation Fates Regulates the Transition From B Lymphoblast to Plasma Cell
Jie HS Zhou, John F Markham, Ken R Duffy, Philip D Hodgkin
FRONTIERS IN IMMUNOLOGY | FRONTIERS MEDIA SA | Published : 2018
In response to external stimuli, naïve B cells proliferate and take on a range of fates important for immunity. How their fate is determined is a topic of much recent research, with candidates including asymmetric cell division, lineage priming, stochastic assignment, and microenvironment instruction. Here we manipulate the generation of plasmablasts from B lymphocytes in vitro by varying CD40 stimulation strength to determine its influence on potential sources of fate control. Using long-term live cell imaging, we directly measure times to differentiate, divide, and die of hundreds of pairs of sibling cells. These data reveal that while the allocation of fates is significantly altered by si..View full abstract
Awarded by National Health and Medical Research Council
Awarded by Science Foundation Ireland
Awarded by Australian Government NHMRC Independent Research Institutes
This work was supported by the National Health and Medical Research Council via Project Grants 1010654 and 1057831, and Program Grant 1054925, and fellowships to PH and Science Foundation Ireland grant No. 12IP1263 to KD. This work was made possible through Victorian State Government Operational Infrastructure Support and Australian Government NHMRC Independent Research Institutes Infrastructure Support Scheme Grant 361646. JZ was supported by an Australian Postgraduate Award. JM was supported by National ICT Australia (NICTA), which was funded by the Australian Research Council and the Australian Department of Broadband, Communications and the Digital Economy. We thank S. Nutt and A. Kallies for Blimp-1-GFP reporter mice.