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 Blood, 15 September 2007, Vol. 110, No. 6, pp. 1950-1959.
Prepublished online as a Blood First Edition Paper on May 25, 2007; DOI 10.1182/blood-2007-01-070003.

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IMMUNOBIOLOGY

Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell homeostasis during lymph node organogenesis

Andrea White1, Damian Carragher1, Sonia Parnell1, Aichi Msaki2, Neil Perkins2, Peter Lane1, Eric Jenkinson1, Graham Anderson1, and Jorge H. Caamaño1

1 Division of Immunity and Infection, Institute for BioMedical Research-Medical Research Council (IBR-MRC) Centre for Immune Regulation, University of Birmingham Medical School, Birmingham; 2 Division of Gene Regulation and Expression, School of Life Sciences, University of Dundee, Dundee, United Kingdom

Lymph nodes provide specialized stromal microenvironments that support the recruitment and organization of T cells and B cells, enabling them to effectively participate in immune responses. While CD4+3– lymphoid tissue inducer cells (LTic's) are known to play a key role in influencing lymph node (LN) development, the mechanisms that regulate the development of stromal organizer cells are unclear. Here, we define an ontogenetic program of lymph node stromal cell maturation in relation to the requirement for LTic's. We also describe a lymph node reaggregation 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 a (LTa)–deficient embryos shows that LTa-mediated signaling is required to sustain proliferation and survival of stromal cells in vivo. Our data identify LTa-independent and LTa-dependent stages of lymph node development, and provide direct evidence for the role of LTic's during LN organogenesis.


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