Submitted January 24, 2007
Accepted May 11, 2007
Lymphotoxin-alpha-dependent and -independent signals regulate stromal organiser cell homeostasis during lymph node organogenesis
Andrea White, Damian Carragher, Sonia Parnell, Aichi Msaki, Neil Perkins, Peter Lane, Eric Jenkinson, Graham Anderson, and Jorge H. Caamano*
Division of Immunity and Infection, IBR-MRC Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom
Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom
* Corresponding author; email: j.caamano{at}bham.ac.uk.
Lymph nodes provide specialised stromal microenvironments that support the recruitment and organisation of T-cells and B-cells, enabling them to effectively participate in immune responses. While CD4+3- lymphoid tissue inducer cells (LTic) are known to play a key role in influencing lymph node development, the mechanisms that regulate the development of stromal organiser cells are unclear. Here, we define an ontogenetic programme of lymph node stromal cell maturation in relation to the requirement for LTic. We also describe a lymph node re-aggregation assay to study cell-cell interactions and lymphocyte recruitment to these organs that reproduces the in vivo events during lymph node development. In addition, analysis of the lymph node anlagen in normal and Lymphotoxin 
-deficient embryos shows that LT-mediated signalling has a homeostatic function on stromal cells in vivo. Our data identify LT-independent and LT-dependent stages of lymph node development, and provide direct evidence for the role of LTic during LN organogenesis.
