  The ability of the adaptive immune system to respond to arbitrary pathogens
stems from the broad diversity of immune cell surface receptors (TCRs). This
diversity originates in a stochastic DNA editing process (VDJ recombination)
that acts each time a new immune cell is created from a stem cell. By analyzing
T cell sequence repertoires taken from the blood and thymus of mice of
different ages, we quantify the significant changes in this process that occur
in development from embryo to young adult. We find a rapid increase with age in
the number of random insertions in the VDJ recombination process, leading to a
dramatic increase in diversity. Since the blood accumulates thymic output over
time, blood repertoires are mixtures of different statistical recombination
processes and, by unraveling the mixture statistics, we can obtain a clear
picture of the time evolution of the early immune system. Sequence repertoire
analysis also allows us to detect the effect of selection on the output of the
VDJ recombination process. The effects we find are nearly identical between
thymus and blood, suggesting that they mainly reflect selection for proper
folding of the TCR receptor protein.
