Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis Journal Article

Authors: Kennedy, D. E.; Knight, K. L.
Article Title: Inflammatory Changes in Bone Marrow Microenvironment Associated with Declining B Lymphopoiesis
Abstract: B lymphopoiesis arrests precipitously in rabbits such that by 2-4 mo of age, before sexual maturity, little to no B lymphopoiesis occurs in the bone marrow (BM). Previously, we showed that in mice, adipocytes inhibit B lymphopoiesis in vitro by inducing inflammatory myeloid cells, which produce IL-1beta. In this study, we characterized rabbit BM after the arrest of B lymphopoiesis and found a dramatic increase in fat, increased CD11b+ myeloid cells, and upregulated expression of the inflammatory molecules, IL-1beta and S100A9, by the myeloid cells. We added BM fat, CD11b+ myeloid cells, and recombinant S100A9 to B lymphopoiesis cultures and found that they inhibited B lymphopoiesis and enhanced myelopoiesis. Unlike IL-1beta, which inhibits B lymphopoiesis by acting on early lymphoid progenitors, S100A9 inhibits B lymphopoiesis by acting on myeloid cells and promoting the release of inflammatory molecules, including IL-1beta. Many molecules produced by adipocytes activate the NLRP3 inflammasome, and the NLRP3 inhibitor, glibenclamide, restored B lymphopoiesis and minimized induction of myeloid cells induced by adipocyte-conditioned medium in vitro. We suggest that fat provides an inflammatory microenvironment in the BM and promotes/activates myeloid cells to produce inflammatory molecules such as IL-1beta and S100A9, which negatively regulate B lymphopoiesis.
Journal Title: Journal of immunology (Baltimore, Md.: 1950)
Volume: 198
Issue: 9
ISSN: 1550-6606; 0022-1767
Publisher: by The American Association of Immunologists, Inc  
Journal Place: United States
Date Published: 2017
Start Page: 3471
End Page: 3479
Language: eng
Notes: LR: 20170519; CI: Copyright (c) 2017; GR: F31 AG047817/AG/NIA NIH HHS/United States; GR: R01 AI068390/AI/NIAID NIH HHS/United States; JID: 2985117R; 0 (Antigens, CD11b); 0 (Calgranulin B); 0 (Interleukin-1beta); 0 (NLR Family, Pyrin Domain-Containing 3 Protein); SX6K58TVWC (Glyburide); NIHMS857408; PMCR: 2018/05/01; 2016/09/21 [received]; 2017/02/27 [accepted]; ppublish