title: B Cell Development in the Bone Marrow Is Regulated by Homeostatic Feedback Exerted by Mature B Cells.
abstract: Cellular homeostasis in the B cell compartment is strictly imposed to balance cell production and cell loss. However, it is not clear whether B cell development in the bone marrow is an autonomous process or subjected to regulation by the peripheral B cell compartment. To specifically address this question, we used mice transgenic for human CD20, where effective depletion of B lineage cells is obtained upon administration of mouse anti-human CD20 antibodies, in the absence of any effect on other cell lineages and/or tissues. We followed the kinetics of B cell return to equilibrium by BrdU labeling and flow cytometry and analyzed the resulting data by mathematical modeling. Labeling was much faster in depleted mice. Compared to control mice, B cell-depleted mice exhibited a higher proliferation rate in the pro-/pre-B compartment, and higher cell death and lower differentiation in the immature B cell compartment. We validated the first result by analysis of the expression of Ki67, the nuclear protein expressed in proliferating cells, and the second using Annexin V staining. Collectively, our results suggest that B lymphopoiesis is subjected to homeostatic feedback mechanisms imposed by mature B cells in the peripheral compartment.
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat-Gan , Israel.
authors.forename: Gitit
authors.initials: G
authors.lastname: Shahaf
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology , Haifa , Israel.
authors.forename: Simona
authors.initials: S
authors.lastname: Zisman-Rozen
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology , Haifa , Israel.
authors.forename: David
authors.initials: D
authors.lastname: Benhamou
authors.affiliation: Department of Immunology, Rappaport Faculty of Medicine, Technion - Israel Institute of Technology , Haifa , Israel.
authors.forename: Doron
authors.initials: D
authors.lastname: Melamed
authors.affiliation: The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University , Ramat-Gan , Israel.
authors.forename: Ramit
authors.initials: R
authors.lastname: Mehr
keywords: B lymphocytes; BrdU; computer simulation; homeostatic feedback; mathematical modeling