title: Ageing adversely affects the migration and function of marginal zone B cells.
abstract: Marginal zone (MZ) B cells are positioned within the spleen to capture blood-borne antigen and immune complexes and deliver them to follicular dendritic cells in the B-cell follicles. We show that within the spleens of aged mice antigen capture by MZ B cells, and their ability to shuttle between the follicle and MZ, were impaired. The ability of aged MZ B cells to migrate towards the MZ chemoattractant sphingosine-1-phosphate was increased, suggesting that aged MZ B cells had a greater propensity to be retained within the MZ. An extrinsic impairment in aged B-cell migration towards the MZ was demonstrated using bone marrow chimeras. The follicular shuttling of MZ B cells derived from either young or aged bone marrow was similarly reduced in aged recipient spleens, showing that ageing effects on splenic stromal cells were responsible for the impaired follicular shuttling of MZ B cells. MZ B cells rapidly mount T-cell-independent (TI) antibody-responses to microbial polysaccharide antigen. In aged mice the ability to produce immunoglobulins in response to the TI type 1 antigen TNP-LPS was impaired. These ageing-related changes to the MZ and MZ B cells have implications for the clearance of blood-borne pathogens. Indeed elderly people have increased susceptibility to Streptococcus pneumoniae, a TI antigen, and decreased responses to vaccination. A thorough analysis of the mechanisms that underpin the ageing-related decline in the status of the MZ and MZ B cells will help the design of novel treatments to improve immunity in the elderly.
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Midlothian, UK.
authors.forename: Vivian M
authors.identifier: 0000-0002-2013-2559
authors.initials: VM
authors.lastname: Turner
authors.affiliation: The Roslin Institute and Royal (Dick) School of Veterinary Sciences, University of Edinburgh, Midlothian, UK.
authors.forename: Neil A
authors.identifier: 0000-0001-7395-1796
authors.initials: NA
authors.lastname: Mabbott
mesh_terms: D000367:Age Factors; D000375:Aging / Q000097:blood / Q000276:immunology*; D000818:Animals; D000955:Antigens, T-Independent / Q000097:blood / Q000276:immunology; D016175:B-Lymphocyte Subsets / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D016026:Bone Marrow Transplantation; D049109:Cell Proliferation; D002478:Cells, Cultured; D054382:Chemokine CXCL13 / Q000494:pharmacology; D002633:Chemotaxis / Q000187:drug effects; D005260:Female; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008246:Lysophospholipids / Q000494:pharmacology; D008810:Mice, Inbred C57BL; D010641:Phenotype; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D017154:Stromal Cells / Q000276:immunology; D018183:Transplantation Chimera
chemical_list: D000955:Antigens, T-Independent; D054382:Chemokine CXCL13; D008070:Lipopolysaccharides; D008246:Lysophospholipids; C048761:trinitrophenyl-lipopolysaccharide; C060506:sphingosine 1-phosphate; D013110:Sphingosine
keywords: B cells; T-independent responses; ageing; marginal zone; spleen