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Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway.

Type of publication Peer-reviewed
Publikationsform Original article (peer-reviewed)
Publication date 2010
Author Kumar Varsha, Scandella Elke, Danuser Renzo, Onder Lucas, Nitschké Maximilian, Fukui Yoshinori, Halin Cornelia, Ludewig Burkhard, Stein Jens V,
Project Examining the function of lymphoid organ structure during antiviral immune responses using microscopic and mesoscopic imaging
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Original article (peer-reviewed)

Journal Blood
Volume (Issue) 115(23)
Page(s) 4725 - 33
Title of proceedings Blood
DOI 10.1182/blood-2009-10-250118

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.
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