B-lymphopoiesis is stopped by mobilizing doses of G-CSF and is rescued by overexpression of the anti-apoptotic protein Bcl2

Granulocyte colony-stimulating factor reprograms bone marrow stromal cells to actively suppress B lymphopoiesis in mice

“…Consistent with a previous report, 5 we observed that G-CSF treatment resulted in marked loss of B cells in the bone marrow, which reached its nadir at 7 days and recovered to near normal 7 days after stopping G-CSF ( Figure 1A). To determine whether G-CSF acts in a cell-intrinsic fashion to suppress B lymphopoiesis, we generated Csf3r 2/2 mixed bone marrow chimeras by transplanting a mixture of wild-type and Csf3r 2/2 bone marrow into wild-type recipients.…”

“…To determine which stages of B-cell development were affected, we measured B-cell progenitor populations in the bone marrow ( Figure 1D). Consistent with a prior study of wild type mice, 5 G-CSF treatment of CD68:Csf3r, Csf3r 2/2 transgenic mice resulted in loss of B-cell precursors. Together, these data show that G-CSF acts through a monocytic-cell intermediate to suppress B lymphopoiesis at For personal use only.…”

“…3,4 A recent study showed that G-CSF suppresses B lymphopoiesis in the bone marrow at multiple stages of development, in part by inducing apoptosis of B-cell precursors. 5 B lymphopoiesis is dependent on the production of supportive signals by bone marrow stromal cells, including CXCL12-abundant reticular (CAR) cells, osteoblasts, and other stromal cells. [6][7][8] Whether G-CSF affects the capacity of these stromal cells to support B lymphopoiesis is unknown.…”

Cellular players of hematopoietic stem cell mobilization in the bone marrow niche

“…Furthermore, three recent studies with conditional deletion of the Cxcl12 or Scf genes from mature osteoblasts using Ocn-Cre or the 2.3-kb fragment of the rat collagen 1a (Col2.3)-Cre did not result HSC mobilization [48,57,68]. However, consistent with the observation that G-CSF ablates osteoblasts and medullar B lymphopoiesis [69] (B lymphocyte progenitors need contact with osteoblasts and CXCL12 to develop [70,71]), conditional deletion of Cxcl12 gene in osteoblasts resulted in the loss of medullar B lymphopoiesis [57,68].…”

Continuous blockade of CXCR4 results in dramatic mobilization and expansion of hematopoietic stem and progenitor cells

“…Given the critical role of CXCR4/CXCL12 signaling in B-cell lymphopoiesis, 29,30 we evaluated B-cell subsets in the bone marrow c t r CFU-C / LSK per ml PB no short-or long-term B-cell lineage deficiency was observed (supplemental Figure 1G). Therefore, POL5551 treatment and mediated expansion had no influence on the lineage reconstitution potential of the HSPCs.…”