Home LiteratureArticle Details
PMID: 18037889 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Follicular shuttling of marginal zone B cells facilitates antigen transport.

Nature immunology ·Vol. 9 ·No. 1 ·2008-01-00 ·Pages 54-62

Cinamon G, Zachariah MA, Lam OM, Foss FW, Cyster JG

Abstract

The splenic marginal zone is a site of blood flow, and the specialized B cell population that inhabits this compartment has been linked to the capture and follicular delivery of blood-borne antigens. However, the mechanism of this antigen transport has remained unknown. Here we show that marginal zone B cells were not confined to the marginal zone but continuously shuttled between the marginal zone and follicular areas, such that many of the cells visited a follicle every few hours. Migration to the follicle required the chemokine receptor CXCR5, whereas return to the marginal zone was promoted by the sphingosine 1-phosphate receptors S1P1 and S1P3. Treatment with an S1P1 antagonist caused displacement of marginal zone B cells from the marginal zone. Marginal zone-follicle shuttling of marginal zone B cells provides an efficient mechanism for systemic antigen capture and delivery to follicular dendritic cells.

MeSH Terms
Animals Antigens/blood,metabolism B-Lymphocytes/physiology Biological Transport Dendritic Cells, Follicular/immunology Fingolimod Hydrochloride Mice Mice, Knockout Propylene Glycols/pharmacology Receptors, CXCR5/genetics,physiology Receptors, Lysosphingolipid/antagonists & inhibitors,physiology Sphingosine/analogs & derivatives,pharmacology Sphingosine-1-Phosphate Receptors Spleen/cytology,immunology
Chemicals
Antigens Propylene Glycols Receptors, CXCR5 Receptors, Lysosphingolipid S1pr3 protein, mouse Sphingosine-1-Phosphate Receptors Fingolimod Hydrochloride Sphingosine
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Cinamon Guy
Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California, San Francisco, California 94143, USA.
Zachariah Marcus A
Lam Olivia M
Foss Frank W
Cyster Jason G
References (48)
48 references, click to expand
  1. CXCL13 is required for B1 cell homing, natural antibody production, and body cavity immunity.
    Immunity. 2002 Jan;16(1):67-76 PMID: 11825566
  2. Lymph-borne chemokines and other low molecular weight molecules reach high endothelial venules via specialized conduits while a functional barrier limits access to the lymphocyte microenvironments in lymph node cortex.
    J Exp Med. 2000 Nov 20;192(10):1425-40 PMID: 11085745
  3. A B-cell-homing chemokine made in lymphoid follicles activates Burkitt's lymphoma receptor-1.
    Nature. 1998 Feb 19;391(6669):799-803 PMID: 9486651
  4. Antigens in immunity. XVI. A light and electron microscope study of antigen localization in the rat spleen.
    Immunology. 1971 Aug;21(2):207-24 PMID: 5571538
  5. Analyses of the in vivo trafficking of stoichiometric doses of an anti-complement receptor 1/2 monoclonal antibody infused intravenously in mice.
    J Immunol. 2004 Aug 15;173(4):2297-306 PMID: 15294942
  6. Cyclical modulation of sphingosine-1-phosphate receptor 1 surface expression during lymphocyte recirculation and relationship to lymphoid organ transit.
    J Exp Med. 2005 Jan 17;201(2):291-301 PMID: 15657295
  7. Sphingosine 1-phosphate receptor 1 promotes B cell localization in the splenic marginal zone.
    Nat Immunol. 2004 Jul;5(7):713-20 PMID: 15184895
  8. Sphingosine 1-phosphate and its receptors: an autocrine and paracrine network.
    Nat Rev Immunol. 2005 Jul;5(7):560-70 PMID: 15999095
  9. The sphingosine-1-phosphate (S1P) lysophospholipid receptor S1P3 regulates MAdCAM-1+ endothelial cells in splenic marginal sinus organization.
    J Exp Med. 2004 Dec 6;200(11):1491-501 PMID: 15583019
  10. Marginal-zone B cells.
    Nat Rev Immunol. 2002 May;2(5):323-35 PMID: 12033738
  11. The differential effects of bacterial lipopolysaccharide (LPS) on splenic non-lymphoid cells demonstrated by monoclonal antibodies.
    Immunology. 1986 Jun;58(2):285-90 PMID: 3519443
  12. Expression of the sphingosine 1-phosphate receptor, S1P1, on T-cells controls thymic emigration.
    J Biol Chem. 2004 Apr 9;279(15):15396-401 PMID: 14732704
  13. Phosphorylation and action of the immunomodulator FTY720 inhibits vascular endothelial cell growth factor-induced vascular permeability.
    J Biol Chem. 2003 Nov 21;278(47):47281-90 PMID: 12954648
  14. Sphingosine 1-phosphate receptor agonist FTY720-phosphate causes marginal zone B cell displacement.
    J Leukoc Biol. 2005 Aug;78(2):471-80 PMID: 15894589
  15. Marginal zone B cells transport and deposit IgM-containing immune complexes onto follicular dendritic cells.
    Int Immunol. 2004 Oct;16(10):1411-22 PMID: 15326094
  16. The follicular dendritic cell restricted epitope, FDC-M2, is complement C4; localization of immune complexes in mouse tissues.
    Eur J Immunol. 2002 Jul;32(7):1888-96 PMID: 12115608
  17. Ligand-induced trafficking of the sphingosine-1-phosphate receptor EDG-1.
    Mol Biol Cell. 1999 Apr;10(4):1179-90 PMID: 10198065
  18. Lymphocyte sequestration through S1P lyase inhibition and disruption of S1P gradients.
    Science. 2005 Sep 9;309(5741):1735-9 PMID: 16151014
  19. Lymphocyte capping and lymphocyte migration as associated events in the in vivo antigen trapping process. An electron-microscopic autoradiographic study in the spleen of mice.
    Cell Tissue Res. 1975 Aug 18;161(2):211-7 PMID: 1175205
  20. Synthesis and biological evaluation of gamma-aminophosphonates as potent, subtype-selective sphingosine 1-phosphate receptor agonists and antagonists.
    Bioorg Med Chem. 2007 Jan 15;15(2):663-77 PMID: 17113298
  21. Isolation of the intact white pulp. Quantitative and qualitative analysis of the cellular composition of the splenic compartments.
    Eur J Immunol. 2000 Feb;30(2):626-34 PMID: 10671220
  22. Promotion of lymphocyte egress into blood and lymph by distinct sources of sphingosine-1-phosphate.
    Science. 2007 Apr 13;316(5822):295-8 PMID: 17363629
  23. Markedly impaired humoral immune response in mice deficient in complement receptors 1 and 2.
    Proc Natl Acad Sci U S A. 1996 Apr 16;93(8):3357-61 PMID: 8622941
  24. CXCR5-deficient mice develop functional germinal centers in the splenic T cell zone.
    Eur J Immunol. 2000 Feb;30(2):560-7 PMID: 10671212
  25. Subcapsular encounter and complement-dependent transport of immune complexes by lymph node B cells.
    Nat Immunol. 2007 Sep;8(9):992-1000 PMID: 17660822
  26. Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces.
    Nat Immunol. 2007 Oct;8(10):1076-85 PMID: 17721537
  27. Cells in the marginal zone of the spleen.
    Int Rev Cytol. 1992;132:31-74 PMID: 1555921
  28. Edg-1, the G protein-coupled receptor for sphingosine-1-phosphate, is essential for vascular maturation.
    J Clin Invest. 2000 Oct;106(8):951-61 PMID: 11032855
  29. Mapping pathways downstream of sphingosine 1-phosphate subtype 1 by differential chemical perturbation and proteomics.
    J Biol Chem. 2007 Mar 9;282(10):7254-64 PMID: 17218309
  30. The localization of aggregated human -globulin in the spleens of normal mice.
    Immunology. 1973 Jun;24(6):955-68 PMID: 4123964
  31. Integrin-dependence of lymphocyte entry into the splenic white pulp.
    J Exp Med. 2003 Feb 3;197(3):353-61 PMID: 12566419
  32. Imaging of germinal center selection events during affinity maturation.
    Science. 2007 Jan 26;315(5811):528-31 PMID: 17185562
  33. A chemokine-driven positive feedback loop organizes lymphoid follicles.
    Nature. 2000 Jul 20;406(6793):309-14 PMID: 10917533
  34. Impairment of T-cell-dependent B-cell responses and B-1 cell development in CD19-deficient mice.
    Nature. 1995 Jul 27;376(6538):352-5 PMID: 7543183
  35. Immunosuppressive and anti-angiogenic sphingosine 1-phosphate receptor-1 agonists induce ubiquitinylation and proteasomal degradation of the receptor.
    J Biol Chem. 2007 Mar 23;282(12):9082-9 PMID: 17237497
  36. The lymphocytes of splenic marginal zones: a distinct B-cell lineage.
    Immunol Today. 1982 Nov;3(11):305-7 PMID: 25290472
  37. Chemokines, sphingosine-1-phosphate, and cell migration in secondary lymphoid organs.
    Annu Rev Immunol. 2005;23:127-59 PMID: 15771568
  38. Tipping the gatekeeper: S1P regulation of endothelial barrier function.
    Trends Immunol. 2007 Mar;28(3):102-7 PMID: 17276731
  39. Integrin-mediated long-term B cell retention in the splenic marginal zone.
    Science. 2002 Jul 19;297(5580):409-12 PMID: 12130787
  40. Tumor necrosis factor and the p55TNF receptor are required for optimal development of the marginal sinus and for migration of follicular dendritic cell precursors into splenic follicles.
    Cell Immunol. 2000 Apr 10;201(1):33-41 PMID: 10805971
  41. Absence of marginal zone B cells in Pyk-2-deficient mice defines their role in the humoral response.
    Nat Immunol. 2000 Jul;1(1):31-6 PMID: 10881171
  42. A conduit system distributes chemokines and small blood-borne molecules through the splenic white pulp.
    J Exp Med. 2003 Aug 4;198(3):505-12 PMID: 12900524
  43. Positive selection from newly formed to marginal zone B cells depends on the rate of clonal production, CD19, and btk.
    Immunity. 2000 Jan;12(1):39-49 PMID: 10661404
  44. The sphingosine-1-phosphate receptors S1P1, S1P2, and S1P3 function coordinately during embryonic angiogenesis.
    J Biol Chem. 2004 Jul 9;279(28):29367-73 PMID: 15138255
  45. A putative chemokine receptor, BLR1, directs B cell migration to defined lymphoid organs and specific anatomic compartments of the spleen.
    Cell. 1996 Dec 13;87(6):1037-47 PMID: 8978608
  46. Antigens in immunity. XII. Antigen trapping in the spleen.
    Int Arch Allergy Appl Immunol. 1966;29(4):368-83 PMID: 5934923
  47. Lymphotoxin alpha/beta and tumor necrosis factor are required for stromal cell expression of homing chemokines in B and T cell areas of the spleen.
    J Exp Med. 1999 Jan 18;189(2):403-12 PMID: 9892622
  48. Relation of intra-splenic migration of marginal zone B cells to antigen localization on follicular dendritic cells.
    Immunology. 1984 Aug;52(4):659-69 PMID: 6378770
Article Info
Journal
Nature immunology
Abbr.
Nat Immunol
ISSN
1529-2916
DOI
10.1038/ni1542
Published
2008-01-00
Epub
2007-00-25
Pages
54-62
Language
English
Region
United States
NLM ID
100941354
PMCID
PMC2488964
Subset
IM
Grants
NIAID NIH HHS · R37 AI040098-09 · United States
NIAID NIH HHS · R37 AI040098-08 · United States
NIAID NIH HHS · R37 AI040098-12 · United States
NIAID NIH HHS · R37 AI040098-10 · United States
NIAID NIH HHS · R37 AI040098-11 · United States
NIAID NIH HHS · N01AI40098 · United States
NIAID NIH HHS · R37 AI040098 · United States
Howard Hughes Medical Institute · United States
Corrections
CommentIn
PMID: 18087249
External Links
PubMed source DOI: 10.1038/ni1542 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2