  A hallmark of the adaptive immune response is the proliferation of
pathogen-specific lymphocytes that leave in their wake a long lived population
of cells that provide lasting immunity. A subject of ongoing investigation is
when during an adaptive immune response those memory cells are produced. In two
ground-breaking studies, Buchholz et al. (Science, 2013) and Gerlach et al.
(Science, 2013) employed experimental methods that allowed identification of
offspring from individual lymphocytes in vivo, which we call clonal data, at a
single time point. Through the development, application and fitting of a
mathematical model, Buchholz et al. (Science, 2013) concluded that, if memory
is produced during the expansion phase, memory cell precursors are made before
the effector cells that clear the original pathogen. We sought to determine the
general validity and power of the modeling approach introduced in Buchholz et
al. (Science, 2013) for quickly evaluating differentiation networks by adapting
it to make it suitable for drawing inferences from more readily available
non-clonal phenotypic proportion time-courses. We first established the method
drew consistent deductions when fit to the non-clonal data in Buchholz et al.
(Science, 2013) itself. We fit a variant of the model to data reported in
Badovinac et al. (J. Immun., 2007), Schlub et al. (Immun. & Cell Bio., 2010),
and Kinjo et al. (Nature Commun., 2015) with necessary simplifications to match
different reported data in these papers. The deduction from the model was
consistent with that in Buchholz et al. (Science, 2013), albeit with
questionable parameterizations. An alternative possibility, supported by the
data in Kinjo et al. (Nature Commun., 2015), is that memory precursors are
created after the expansion phase, which is a deduction not possible from the
mathematical methods provided in Buchholz et al. (Science, 2013).
