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*
Department of Molecular Biology, Princeton University, Princeton, NJ, 08544; and
Fox Chase Cancer Center, Philadelphia, PA 19111
Recent evidence suggests that lymphocyte Ag receptor gene
rearrangement does not always stop after the expression of the first
productively rearranged receptor. Light chain gene rearrangement in B
cells, and 
-chain rearrangement in T cells can continue, which
raises the question: how is allelic exclusion maintained, if at all, in
the face of continued rearrangement? In this and the accompanying
paper, we present comprehensive models of Ag receptor gene
rearrangement and the interaction of this process with clonal
selection. Our B cell model enables us to reconcile observations on the
:
ratio and on allele usage, showing that B cell receptor
gene rearrangement must be a highly ordered, rather than a random,
process. We show that order is exhibited on three levels: a preference
for rearranging rather than light chain genes; a preference to
make secondary rearrangements on the allele that has already been
rearranged, rather than choosing the location of the next rearrangement
at random; and a sequentiality of J segment choice within each
allele. This order, combined with the stringency of negative selection,
is shown to lead to effective allelic exclusion.
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