PMID- 23002443 OWN - NLM STAT- MEDLINE DCOM- 20130109 LR - 20211021 IS - 1550-6606 (Electronic) IS - 0022-1767 (Print) IS - 0022-1767 (Linking) VI - 189 IP - 9 DP - 2012 Nov 1 TI - Adipocyte-derived soluble factor(s) inhibits early stages of B lymphopoiesis. PG - 4379-86 LID - 10.4049/jimmunol.1201176 [doi] AB - B lymphopoiesis declines with age, and in rabbits this occurs by 8 wk of age. We found that CFU fibroblasts (CFU-Fs) in the bone marrow (BM) decrease 10-fold by a few weeks of age and that the CFU-Fs preferentially differentiate into adipocytes instead of osteoblasts. BM becomes filled with fat spaces during this time, making rabbit a unique model to study the effects of accelerated fat accumulation on B lymphopoiesis. We show that adipocytes of both rabbit and human secrete a soluble factor(s) that inhibits B lymphopoiesis, and we tested if this inhibition was due to effects on the BM stroma or hematopoietic progenitors. Pretreatment of BM mononuclear cells with adipocyte conditioned medium dramatically inhibited their differentiation into proB cells in cocultures with OP9 stromal cells. In contrast, pretreatment of OP9 stromal cells with adipocyte conditioned medium had no effect on B lymphopoiesis. Using human hematopoietic stem cells, we show that inhibition by the adipocyte-derived factor occurred at the common lymphoid progenitor to preproB cell stage. We propose that the age-related decline in B lymphopoiesis is due to a decrease in CFU-Fs, an increase in adipocytes, and an adipocyte-derived factor that blocks B lymphopoiesis at the common lymphoid progenitor to preproB cell stage. FAU - Bilwani, Fareena A AU - Bilwani FA AD - Department of Microbiology and Immunology, Loyola University Chicago, Maywood, IL 60153, USA. FAU - Knight, Katherine L AU - Knight KL LA - eng GR - R01 AI068390/AI/NIAID NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20120921 PL - United States TA - J Immunol JT - Journal of immunology (Baltimore, Md. : 1950) JID - 2985117R RN - 0 (FABP4 protein, human) RN - 0 (Fatty Acid-Binding Proteins) RN - 0 (Growth Inhibitors) SB - IM MH - Adipocytes/*physiology MH - Animals MH - B-Lymphocyte Subsets/*cytology/*immunology/metabolism MH - Cell Line MH - Fatty Acid-Binding Proteins/*physiology MH - Fibroblasts/cytology/immunology/metabolism MH - Growth Inhibitors/*physiology MH - Humans MH - Lymphopoiesis/*immunology MH - Osteoblasts/cytology/immunology/metabolism MH - Rabbits MH - Stem Cells/cytology/immunology/metabolism/physiology PMC - PMC3483032 MID - NIHMS403412 COIS- DISCLOUSRE: The authors have no conflicting financial interests. EDAT- 2012/09/25 06:00 MHDA- 2013/01/10 06:00 PMCR- 2013/11/01 CRDT- 2012/09/25 06:00 PHST- 2012/09/25 06:00 [entrez] PHST- 2012/09/25 06:00 [pubmed] PHST- 2013/01/10 06:00 [medline] PHST- 2013/11/01 00:00 [pmc-release] AID - jimmunol.1201176 [pii] AID - 10.4049/jimmunol.1201176 [doi] PST - ppublish SO - J Immunol. 2012 Nov 1;189(9):4379-86. doi: 10.4049/jimmunol.1201176. Epub 2012 Sep 21.