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Oxysterol gradient generation by lymphoid stromal cells guides activated B cell movement during humoral responses

Yi, Tangsheng and Wang, Xiaoming and Kelly, Lisa M. and An, Jinping and Xu, Ying and Sailer, Andreas and Gustafsson, Jan-Ake and Russell, David W. and Cyster, Jason G. (2012) Oxysterol gradient generation by lymphoid stromal cells guides activated B cell movement during humoral responses. Immunity, 37 (3). pp. 535-548. ISSN 1074-7613

Abstract

7α,25-dihydroxycholesterol (7α,25-OHC) was recently identified as an EBI2(GPR183) ligand; however, the cellular sources of this oxysterol are undefined. 7α,25-OHC is synthesized from cholesterol by the stepwise actions of CH25H and CYP7B1, and is further metabolized to a 3-oxo derivative by HSD3B7. We show that CYP7B1 and HSD3B7 control EBI2-ligand concentration in lymphoid tissues. CH25H and CYP7B1 are abundant at the B cell follicle perimeter whereas HSD3B7 is abundant in the T zone. Lymphoid stromal cells are the main EBI2-ligand producers and also mediate ligand inactivation. Dendritic cell-HSD3B7 is additionally needed to keep T zone ligand concentrations low and to aid activated B cell positioning. CYP7B1-deficiency results in defective plasma cell responses. These findings establish that CYP7B1 and HSD3B7 have essential roles in controlling oxysterol production outside the liver and
they suggest multiple lymphoid resident cells cooperate to form the 7α,25-OHC gradients required for B cell responses.

Item Type: Article
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Keywords: oxysterol, EBI2, CYP7B1, HSD3B7, B cell migration
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Date Deposited: 13 Oct 2015 13:14
Last Modified: 13 Oct 2015 13:14
URI: https://oak.novartis.com/id/eprint/6718

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