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

Kumar, Varsha; Scandella, Elke; Danuser, Renzo; Onder, Lucas; Nitschké, Maximilian; Fukui, Yoshinori; Halin, Cornelia; Ludewig, Burkhard; Stein, Jens V (2010). Global lymphoid tissue remodeling during a viral infection is orchestrated by a B cell-lymphotoxin-dependent pathway. Blood, 115(23), pp. 4725-33. Washington, D.C.: American Society of Hematology 10.1182/blood-2009-10-250118

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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.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute
UniBE Contributor:	Kumar, Varsha, Danuser, Renzo, Stein, Jens Volker
ISSN:	0006-4971
Publisher:	American Society of Hematology
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 14:07
Last Modified:	05 Dec 2022 14:00
Publisher DOI:	10.1182/blood-2009-10-250118
PubMed ID:	20185585
Web of Science ID:	000278635900019
URI:	https://boris.unibe.ch/id/eprint/247 (FactScience: 197095)