Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.

Specialized B cells residing in the splenic marginal zone (MZ) continuously survey the blood for antigens and are important for immunity to systemic infections. However, the cues that uniquely attract cells to the MZ have not been defined. Previous work demonstrated that mice deficient in cannabinoi...

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Main Authors: Muppidi, JR, Arnon, T, Bronevetsky, Y, Veerapen, N, Tanaka, M, Besra, G, Cyster, J
Format: Journal article
Language:English
Published: 2011
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author Muppidi, JR
Arnon, T
Bronevetsky, Y
Veerapen, N
Tanaka, M
Besra, G
Cyster, J
author_facet Muppidi, JR
Arnon, T
Bronevetsky, Y
Veerapen, N
Tanaka, M
Besra, G
Cyster, J
author_sort Muppidi, JR
collection OXFORD
description Specialized B cells residing in the splenic marginal zone (MZ) continuously survey the blood for antigens and are important for immunity to systemic infections. However, the cues that uniquely attract cells to the MZ have not been defined. Previous work demonstrated that mice deficient in cannabinoid receptor 2 (CB2) have decreased numbers of MZ B cells but it has been unclear whether CB2 regulates MZ B cell development or positioning. We show that MZ B cells are highly responsive to the CB2 ligand 2-arachidonylglycerol (2-AG) and that CB2 antagonism rapidly displaces small numbers of MZ B cells to the blood. Antagonism for longer durations depletes MZ B cells from the spleen. In mice deficient in sphingosine-1-phosphate receptor function, CB2 antagonism causes MZ B cell displacement into follicles. Moreover, CB2 overexpression is sufficient to position B cells to the splenic MZ. These findings establish a role for CB2 in guiding B cells to the MZ and in preventing their loss to the blood. As a consequence of their MZ B cell deficiency, CB2-deficient mice have reduced numbers of CD1d-high B cells. We show that CB2 deficiency results in diminished humoral responses to a CD1d-restricted systemic antigen.
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spelling oxford-uuid:8a5eaa9d-8498-4144-a06c-92eadb14845e2022-03-26T22:31:07ZCannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:8a5eaa9d-8498-4144-a06c-92eadb14845eEnglishSymplectic Elements at Oxford2011Muppidi, JRArnon, TBronevetsky, YVeerapen, NTanaka, MBesra, GCyster, JSpecialized B cells residing in the splenic marginal zone (MZ) continuously survey the blood for antigens and are important for immunity to systemic infections. However, the cues that uniquely attract cells to the MZ have not been defined. Previous work demonstrated that mice deficient in cannabinoid receptor 2 (CB2) have decreased numbers of MZ B cells but it has been unclear whether CB2 regulates MZ B cell development or positioning. We show that MZ B cells are highly responsive to the CB2 ligand 2-arachidonylglycerol (2-AG) and that CB2 antagonism rapidly displaces small numbers of MZ B cells to the blood. Antagonism for longer durations depletes MZ B cells from the spleen. In mice deficient in sphingosine-1-phosphate receptor function, CB2 antagonism causes MZ B cell displacement into follicles. Moreover, CB2 overexpression is sufficient to position B cells to the splenic MZ. These findings establish a role for CB2 in guiding B cells to the MZ and in preventing their loss to the blood. As a consequence of their MZ B cell deficiency, CB2-deficient mice have reduced numbers of CD1d-high B cells. We show that CB2 deficiency results in diminished humoral responses to a CD1d-restricted systemic antigen.
spellingShingle Muppidi, JR
Arnon, T
Bronevetsky, Y
Veerapen, N
Tanaka, M
Besra, G
Cyster, J
Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.
title Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.
title_full Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.
title_fullStr Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.
title_full_unstemmed Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.
title_short Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.
title_sort cannabinoid receptor 2 positions and retains marginal zone b cells within the splenic marginal zone
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