%A Shahaf,Gitit %A Zisman-Rozen,Simona %A Benhamou,David %A Melamed,Doron %A Mehr,Ramit %D 2016 %J Frontiers in Immunology %C %F %G English %K B lymphocytes,BrdU,Computer Simulation,homeostatic feedback,mathematical modeling. %Q %R 10.3389/fimmu.2016.00077 %W %L %M %P %7 %8 2016-March-22 %9 Original Research %+ Prof Ramit Mehr,The Mina and Everard Goodman Faculty of Life Sciences, Bar-Ilan University,Israel,ramit.mehr@biu.ac.il %# %! Homeostatic Feedback in B lymphopoiesis %* %< %T B Cell Development in the Bone Marrow Is Regulated by Homeostatic Feedback Exerted by Mature B Cells %U https://www.frontiersin.org/articles/10.3389/fimmu.2016.00077 %V 7 %0 JOURNAL ARTICLE %@ 1664-3224 %X 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.