Lymphotoxin a-dependent and -independent signals regulate stromal organizer cell homeostasis during lymph node organogenesis.
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.
White
Andrea
A
Division of Immunity and Infection, Instiute for BioMedical Research-Medical Research Council Centre for Immune Regulation, University of Birmingham Medical School, Birmingham, United Kingdom.
Carragher
Damian
D
Parnell
Sonia
S
Msaki
Aichi
A
Perkins
Neil
N
Lane
Peter
P
Jenkinson
Eric
E
Anderson
Graham
G
Caamaño
Jorge H
JH
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation / Q000276:immunology*; D049109:Cell Proliferation; D005333:Fetus; D018507:Gene Expression Regulation, Developmental; D006706:Homeostasis; D053631:Interleukin Receptor Common gamma Subunit; D017493:Leukocyte Common Antigens / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008233:Lymphotoxin-alpha / Q000235:genetics / Q000502:physiology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009924:Organ Culture Techniques; D038081:Organogenesis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017154:Stromal Cells / Q000276:immunology / Q000378:metabolism*
D053631:Interleukin Receptor Common gamma Subunit; D008233:Lymphotoxin-alpha; D012333:RNA, Messenger; D017493:Leukocyte Common Antigens; C516770:Ptprc protein, mouse