title: Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway.
abstract: Adaptive immune responses are characterized by substantial restructuring of secondary lymphoid organs. The molecular and cellular factors responsible for virus-induced lymphoid remodeling are not well known to date. Here we applied optical projection tomography, a mesoscopic imaging technique, for a global analysis of the entire 3-dimensional structure of mouse peripheral lymph nodes (PLNs), focusing on B-cell areas and high endothelial venule (HEV) networks. Structural homeostasis of PLNs was characterized by a strict correlation between total PLN volume, B-cell volume, B-cell follicle number, and HEV length. After infection with lymphocytic choriomeningitis virus, we observed a substantial, lymphotoxin (LT) beta-receptor-dependent reorganization of the PLN microarchitecture, in which an initial B-cell influx was followed by 3-fold increases in PLN volume and HEV network length on day 8 after infection. Adoptive transfer experiments revealed that virus-induced PLN and HEV network remodeling required LTalpha(1)beta(2)-expressing B cells, whereas the inhibition of vascular endothelial growth factor-A signaling pathways had no significant effect on PLN expansion. In summary, lymphocytic choriomeningitis virus-induced PLN growth depends on a vascular endothelial growth factor-A-independent, LT- and B cell-dependent morphogenic pathway, as revealed by an in-depth mesoscopic analysis of the global PLN structure.
authors.affiliation: Theodor Kocher Institute, University of Bern, Bern, Switzerland.
authors.forename: Varsha
authors.initials: V
authors.lastname: Kumar
authors.forename: Elke
authors.initials: E
authors.lastname: Scandella
authors.forename: Renzo
authors.initials: R
authors.lastname: Danuser
authors.forename: Lucas
authors.initials: L
authors.lastname: Onder
authors.forename: Maximilian
authors.initials: M
authors.lastname: Nitschké
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Fukui
authors.forename: Cornelia
authors.initials: C
authors.lastname: Halin
authors.forename: Burkhard
authors.initials: B
authors.lastname: Ludewig
authors.forename: Jens V
authors.initials: JV
authors.lastname: Stein
mesh_terms: D056704:Adaptive Immunity; D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D005786:Gene Expression Regulation / Q000235:genetics / Q000276:immunology; D006706:Homeostasis / Q000235:genetics / Q000276:immunology; D008198:Lymph Nodes / Q000276:immunology* / Q000473:pathology / Q000821:virology; D008216:Lymphocytic Choriomeningitis / Q000235:genetics / Q000276:immunology* / Q000378:metabolism; D008217:Lymphocytic choriomeningitis virus / Q000276:immunology*; D053361:Lymphotoxin alpha1, beta2 Heterotrimer / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology*; D053259:Lymphotoxin beta Receptor / Q000096:biosynthesis / Q000235:genetics / Q000276:immunology; D051379:Mice; D018345:Mice, Knockout; D015398:Signal Transduction / Q000235:genetics / Q000276:immunology; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000276:immunology / Q000378:metabolism
chemical_list: C505699:Ltbr protein, mouse; D053361:Lymphotoxin alpha1, beta2 Heterotrimer; D053259:Lymphotoxin beta Receptor; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse