Progenitor Cell Origin Plays a Role in Fate Choices of Mature B Cells

Abstract

B cells, the Ab-producing cells of the immune system, develop from hematopoietic stem cells (HSCs) through well-defined stages during which Ig genes are rearranged to generate a clonal BCR. Signaling through the BCR plays a role in the subsequent cell fate decisions leading to the generation of three distinct types of B cells: B1, marginal zone, and follicular B cells. Common lymphoid progenitors (CLPs) are descended from HSCs, and although recent observations suggest that CLPs may not be physiological T cell precursors, it is generally accepted that CLPs are obligate progenitors for B cells. In addition, a CLP-like progenitor of unknown significance that lacks expression of c-kit (kit−CLP) was recently identified in the mouse model. In this study, we show that CLPs, kit−CLPs and a population within the lin−Sca1+kit+flt3− HSC compartment generate mature B cell types in different proportions: CLPs and kit−CLPs show a stronger marginal zone /follicular ratio than lin−Sca1+kit+flt3− cells, whereas kit−CLPs show a stronger B1 bias than any other progenitor population. Furthermore, expression of Sca1 on B cells depends on their progenitor origin as B cells derived from CLPs and kit−CLPs express more Sca1 than those derived from lin−Sca1+kit+flt3− cells. These observations indicate a role for progenitor origin in B cell fate choices and suggest the existence of CLP-independent B cell development.