Asynchronous differentiation models explain bone marrow labeling kinetics and predict reflux between the pre- and immature B cell pools

Abstract

B lymphopoiesis has historically been depicted as a unidirectional process, in which cohorts of developing cells transit through successive differentiative stages in an irreversible, synchronous manner. Here, we examine this view by combining kinetic analysis of developing B cell subsets in the bone marrow with mathematical modeling. Our bromo-deoxyuridine (BrdU) labeling data are incompatible with B cell development being a synchronous process, because labeling curves are non-linear. Moreover, we show that B cell development may not be completely unidirectional, because our results support the possibility of a phenotypic 'reflux' among the immature to the pre-B cell subsets.