Progenitor cell origin plays a role in fate choices of mature B cells.
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.
Fossati
Valentina
V
Department of Gene and Cell Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Kumar
Ritu
R
Snoeck
Hans-Willem
HW
D000818:Animals; D001202:Ascitic Fluid / Q000166:cytology / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000166:cytology* / Q000276:immunology*; D001854:Bone Marrow Cells / Q000166:cytology / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D019070:Cell Lineage / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008822:Mice, Transgenic; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000276:immunology*; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology
D019009:Proto-Oncogene Proteins c-kit