Stochastic or Asymmetric Fate Determination?

Science Signaling  24 Jan 2012:
Vol. 5, Issue 208, pp. ec31
DOI: 10.1126/scisignal.2002875

During an adaptive immune response, B lymphocytes rapidly divide and differentiate into effector cell populations, including antibody-secreting plasmablasts and memory B cells. Many also change the class of antibody they secrete, through a process called isotype switching. During this process, some cells die. Whether cells acquire these different fates in a stochastic or programmed manner, however, is unclear. Duffy et al. used single-cell tracking to determine the times to division, differentiation into a plasmablast, isotype switching, and death of stimulated B lymphocytes. Statistical analysis and mathematical modeling revealed that these cell-fate decisions appear to be the result of random clocks: Which clock went off first (division, differentiation, or death) determined the fate of the cell. Barnett et al. sought to determine whether asymmetrical cell division, which is thought to contribute to effector cell-fate decisions in T cells, may be at work in B lymphocytes. Indeed, factors important for the initiation and maintenance of germinal center B lymphocyte identity, along with an ancestral polarity protein, were asymmetrically distributed and maintained their asymmetry during cell division.

K. R. Duffy, C. J. Wellard, J. F. Markham, J. H. S. Zhou, R. Holmberg, E. D. Hawkins, J. Hasbold, M. R. Dowling, P. D. Hodgkin, Activation-induced B cell fates are selected by intracellular stochastic competition. Science 335, 338–341 (2012). [Abstract] [Full Text]

B. E. Barnett, M. L. Ciocca, R. Goenka, L. G. Barnett, J. Wu, T. M. Laufer, J. K. Burkhardt, M. P. Cancro, S. L. Reiner, Asymmetric B cell division in the germinal center reaction. Science 335, 342–344 (2012). [Abstract] [Full Text]