Progenitor cell origin plays a role in fate choices of mature B cells

V Fossati, R Kumar, HW Snoeck - The journal of immunology, 2010 - journals.aai.org
V Fossati, R Kumar, HW Snoeck
The journal of immunology, 2010journals.aai.org
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 …
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.
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