title: Immune complex relay by subcapsular sinus macrophages and noncognate B cells drives antibody affinity maturation.
abstract: Subcapsular sinus (SCS) macrophages capture antigens from lymph and present them intact for B cell encounter and follicular delivery. However, the properties of SCS macrophages are poorly defined. Here we show SCS macrophage development depended on lymphotoxin-alpha1beta2, and the cells had low lysosomal enzyme expression and retained opsonized antigens on their surface. Intravital imaging revealed immune complexes moving along macrophage processes into the follicle. Moreover, noncognate B cells relayed antigen opsonized by newly produced antibodies from the subcapsular region to the germinal center, and affinity maturation was impaired when this transport process was disrupted. Thus, we characterize SCS macrophages as specialized antigen-presenting cells functioning at the apex of an antigen transport chain that promotes humoral immunity.
authors.affiliation: [1] Howard Hughes Medical Institute and Department of Microbiology and Immunology, University of California San Francisco (UCSF), California, USA. [2] Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
authors.forename: Tri Giang
authors.initials: TG
authors.lastname: Phan
authors.forename: Jesse A
authors.initials: JA
authors.lastname: Green
authors.forename: Elizabeth E
authors.initials: EE
authors.lastname: Gray
authors.forename: Ying
authors.initials: Y
authors.lastname: Xu
authors.forename: Jason G
authors.initials: JG
authors.lastname: Cyster
mesh_terms: D000818:Animals; D000906:Antibodies / Q000276:immunology*; D000915:Antibody Affinity; D000936:Antigen-Antibody Complex / Q000276:immunology*; D000938:Antigen-Presenting Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000954:Antigens, Surface / Q000276:immunology; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D004705:Endocytosis; D005434:Flow Cytometry; D018858:Germinal Center / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology*; D008233:Lymphotoxin-alpha / Q000378:metabolism; D008247:Lysosomes / Q000201:enzymology; D008264:Macrophages / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D008815:Mice, Inbred Strains; D008856:Microscopy, Fluorescence; D009113:Muramidase / Q000378:metabolism; D009895:Opsonin Proteins / Q000276:immunology; D010447:Peptide Hydrolases / Q000378:metabolism
chemical_list: D000906:Antibodies; D000936:Antigen-Antibody Complex; D000954:Antigens, Surface; D008233:Lymphotoxin-alpha; D009895:Opsonin Proteins; D009113:Muramidase; D010447:Peptide Hydrolases