title: Cannabinoid receptor 2 positions and retains marginal zone B cells within the splenic marginal zone.
abstract: 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.
authors.affiliation: Howard Hughes Medical Institute, Department of Microbiology and Immunology, and Department of Medicine, University of California, San Francisco, San Francisco, CA, USA.
authors.forename: Jagan R
authors.initials: JR
authors.lastname: Muppidi
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.forename: Yelena
authors.initials: Y
authors.lastname: Bronevetsky
authors.forename: Natacha
authors.initials: N
authors.lastname: Veerapen
authors.forename: Masato
authors.initials: M
authors.lastname: Tanaka
authors.forename: Gurdyal S
authors.initials: GS
authors.lastname: Besra
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D000906:Antibodies / Q000378:metabolism; D015703:Antigens, CD / Q000235:genetics / Q000276:immunology; D001095:Arachidonic Acids / Q000378:metabolism; D001402:B-Lymphocytes / Q000166:cytology* / Q000276:immunology* / Q000502:physiology; D063388:Endocannabinoids; D005989:Glycerides / Q000378:metabolism; D056724:Immunity, Humoral; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D043885:Receptor, Cannabinoid, CB2 / Q000235:genetics / Q000378:metabolism*; D049349:Receptors, Lysosphingolipid / Q000235:genetics / Q000378:metabolism; D013154:Spleen / Q000166:cytology* / Q000276:immunology
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D001095:Arachidonic Acids; D063388:Endocannabinoids; D005989:Glycerides; D043885:Receptor, Cannabinoid, CB2; D049349:Receptors, Lysosphingolipid; C094503:glyceryl 2-arachidonate