title: Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress.
abstract: The splenic marginal zone is a unique microenvironment where resident immune cells are exposed to the open blood circulation. Even though it has an important role in responses against blood-borne antigens, lymphocyte migration in the marginal zone has not been intravitally visualized due to challenges associated with achieving adequate imaging depth in this abdominal organ. Here we develop a two-photon microscopy procedure to study marginal zone and follicular B-cell movement in the live mouse spleen. We show that marginal zone B cells are highly motile and exhibit long membrane extensions. Marginal zone B cells shuttle between the marginal zone and follicles with at least one-fifth of the cells exchanging between compartments per hour, a behaviour that explains their ability to deliver antigens rapidly from the open blood circulation to the secluded follicles. Follicular B cells also transit from follicles to the marginal zone, but unlike marginal zone B cells, they fail to undergo integrin-mediated adhesion, become caught in fluid flow and are carried into the red pulp. Follicular B-cell egress via the marginal zone is sphingosine-1-phosphate receptor-1 (S1PR1)-dependent. This study shows that marginal zone B cells migrate continually between marginal zone and follicles and establishes the marginal zone as a site of S1PR1-dependent B-cell exit from follicles. The results also show how adhesive differences of similar cells critically influence their behaviour in the same microenvironment.
authors.affiliation: Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA.
authors.forename: Tal I
authors.initials: TI
authors.lastname: Arnon
authors.forename: Robert M
authors.initials: RM
authors.lastname: Horton
authors.forename: Irina L
authors.initials: IL
authors.lastname: Grigorova
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology* / Q000187:drug effects / Q000276:immunology; D002448:Cell Adhesion / Q000276:immunology; D002465:Cell Movement / Q000187:drug effects / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000166:cytology / Q000276:immunology; D000068876:Fingolimod Hydrochloride; D007166:Immunosuppressive Agents / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D011409:Propylene Glycols / Q000494:pharmacology; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013154:Spleen / Q000166:cytology* / Q000276:immunology
chemical_list: D007166:Immunosuppressive Agents; D011409:Propylene Glycols; D000068876:Fingolimod Hydrochloride; D013110:Sphingosine