Blood. 2016 May 17. pii: blood-2016-01-693887. [Epub ahead of print]

Macrophage colony-stimulating factor receptor marks and regulates a fetal myeloid-primed B cell progenitor in mouse.

Zriwil A¹, Böiers C², Wittmann L¹, Green JC³, Woll PS⁴, Jacobsen SE⁴, Sitnicka E⁵.

Abstract

While it is well established that unique B cell lineages develop through distinct regulatory mechanisms during embryonic development, much less is understood about the differences between embryonic and adult B-cell progenitor cells, likely to underpin the genetics and biology of infant and childhood PreB acute lymphoblastic leukemia (PreB-ALL), initiated by distinct leukemia-initiating translocations during embryonic development. Herein, we establish that a distinct subset of the earliest CD19⁺ B-cell progenitors emerging in the E13.5 mouse fetal liver express the Colony Stimulating Factor-1 receptor (CSF1R), previously thought to be expressed and play a lineage-restricted role in development of myeloid lineages, and macrophages in particular. These early embryonic CSF1R⁺CD19⁺ ProB cells also express multiple other myeloid genes, and in line with this possess residual myeloid as well as B cell, but not T cell lineage potential. Notably, these CSF1R⁺ myeloid-primed ProB cells are uniquely present in a narrow window of embryonic fetal liver hematopoiesis and do not persist in adult bone marrow. Moreover, analysis of CSF1R-deficient mice establishes a distinct role of CSF1R in fetal B-lymphopoiesis. CSF1R⁺ myeloid-primed embryonic ProB cells are relevant for infant and childhood PreB-ALLs which frequently have a bi-phenotypic B-myeloid phenotype, and in which CSF1R-rearrangements have recently been reported.