Abstract:IntroductionThe period of immune deficiency after high-dose chemotherapy and bone marrow (BM) transplantation (BMT) results in significant morbidity and mortality. 1 Whereas early recovery of innate immunity (granulocytes, monocytes/macrophages and natural killer [NK] cells) results in reconstitution of protective immunity against many bacterial pathogens, the levels of functional lymphocytes (components of adaptive immunity) frequently remain abnormal for many months or years. 2 Low levels of B cells and immu… Show more
“…13,38,39 Notably, compared with WT mice a reduction was observed in total PB reconstitution in Fl Ϫ/Ϫ mice at 16 weeks after transplantation (3.6-fold; Figure 2B). This was almost entirely due to a failure to regenerate primarily B cells and partially T cells in the absence of FL, in agreement with recent studies, 19,40 whereas myeloid reconstitution, representing the best measure of HSC activity because of the short half-life of the myeloid lineage, was not significantly reduced in peripheral blood ( Figure 2B) or in BM ( Figure 2C) of Fl Ϫ/Ϫ recipients. Furthermore, the regeneration of donor-derived LSKCD150 ϩ HSC compartment was not different in Fl Ϫ/Ϫ and WT recipients ( Figure 2D).…”
Section: Role Of Flt3 Ligand In Hsc Maintenance and Expansion After Tsupporting
“…13,38,39 Notably, compared with WT mice a reduction was observed in total PB reconstitution in Fl Ϫ/Ϫ mice at 16 weeks after transplantation (3.6-fold; Figure 2B). This was almost entirely due to a failure to regenerate primarily B cells and partially T cells in the absence of FL, in agreement with recent studies, 19,40 whereas myeloid reconstitution, representing the best measure of HSC activity because of the short half-life of the myeloid lineage, was not significantly reduced in peripheral blood ( Figure 2B) or in BM ( Figure 2C) of Fl Ϫ/Ϫ recipients. Furthermore, the regeneration of donor-derived LSKCD150 ϩ HSC compartment was not different in Fl Ϫ/Ϫ and WT recipients ( Figure 2D).…”
Section: Role Of Flt3 Ligand In Hsc Maintenance and Expansion After Tsupporting
“…Previous studies have demonstrated that Flt3-Ligand-deficient mice have a reduction in B-cell progenitors in the E14.5 FL. 35 Here we reproduced this finding in Flt3 receptor-deficient (Flk2 2/2 ) mice, and found that although the FL cellularity was not affected (Figure 5B), the frequency of ProB cells was further and dramatically reduced in the E14.5 FL of Flk2 2/2 Csf1r 2/2 double-deficient embryos, when compared with Csf1r 2/2 and Flk2 2/2 single-deficient embryos ( Figure 5C). This finding supports that CSF1R and FLT3 have complementary and critical roles in regulation of the emergence of fetal B-cell progenitors.…”
Section: Concomitant Loss Of Flt3 and Csf1r Leads To A Severe Reductisupporting
Key Points
CSF1R is expressed on the earliest fetal B-cell progenitors, and CSF1R deficiency impairs fetal B-cell development. CSF1R+ fetal ProB cells have a B-myeloid gene signature and possess B and myeloid potential.
“…This, however, does not rule out a more crucial role of FL in the GM lineage. In the case of B lymphopoiesis, FL has been shown to have a critical role in B-cell generation after BM transplantation, 42 becomes increasingly important with age, and-most notably IL-7-independent B lymphopoiesis-is strictly FL dependent. 10 Thus, further studies might better reveal conditions in which FL is critically involved in generation and regeneration of cells of the GM lineage.…”
Section: Role Of Flt3 In Early Myelopoiesis 5065mentioning
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