Related Experiment Video
Updated: May 24, 2026
Generation of Lymph Node-fat Pad Chimeras for the Study of Lymph Node Stromal Cell Origin
Published on: December 16, 2013
Expression pattern changes and function of RANKL during mouse lymph node microarchitecture development
Machiko Sugiyama1, Gaku Nakato, Toshi Jinnohara
1Department of Supramolecular Biology, International Graduated School of Arts and Science Yokohama city university, Yokohama, Kanagawa 230-0045, Japan.
Insights
Receptor activator of nuclear factor kappa-B ligand (RANKL) is critical for lymph node (LN) development. Blocking RANKL function in fetal mice completely inhibited LN development and perturbed B-cell follicle formation.
Area of Science:
- Immunology
- Developmental Biology
- Anatomy
Background:
- Receptor activator of nuclear factor kappa-B ligand (RANKL) plays a role in immune system development.
- Its expression pattern shifts during the development of fetal peripheral lymphoid organs, specifically in lymph node (LN) anlagen.
Purpose of the Study:
- To investigate the functional role of RANKL during the development of mouse fetal peripheral lymphoid organs.
- To understand the impact of RANKL expression changes on lymph node development.
Main Methods:
- Examined RANKL expression during fetal lymphoid organ development in mice.
- Blocked RANKL function using anti-RANKL antibodies administered to pregnant mice and directly into the amniotic space.
- Observed effects on lymph node anlagen development, B-cell follicle formation, and high endothelial venule differentiation postnatally.
Main Results:
- A shift in RANKL expression was observed during the transition from lymphoid tissue inducer (LTi) to lymphoid tissue organizer (LTo) cells in LN anlagen.
- Complete blockade of RANKL function during a critical fetal period (13.5-16.5 dpc) completely inhibited LN anlagen development.
- Direct injection of anti-RANKL antibodies into the amniotic space perturbed B-cell follicle formation and high endothelial venule differentiation.
Conclusions:
- RANKL expression on LTi cells during early LN development is essential for LN microarchitecture formation.
- RANKL signaling is a critical regulator of lymph node organogenesis.
Abstract:
Receptor activator of nuclear factor kappa-B ligand (RANKL) expression was examined during the development of mouse fetal peripheral lymphoid organs. A shift in the expression pattern was detected during the transition from lymphoid tissue inducer (LTi) cells to lymphoid tissue organizer (LTo) cells in the lymph node (LN) anlagen but not in the Peyer's patch anlagen. In order to understand the functional impact of these changes in the fetal expression of RANKL, the RANKL function was blocked by a blocking antibody. Excess anti-RANKL antibody was administered to pregnant mice between 13.5 and 16.5 dpc and was found to completely block LN anlagen development, suggesting that RANKL function during this period is critical for LN development. In addition, small amounts of anti-RANKL antibodies were injected directly into the amniotic space at 13.5 dpc, resulting in perturbed B-cell follicle formation and high endothelial venule differentiation after birth. These results suggest that RANKL expression on LTi cells during the early phase of LN development is critical for the development LN microarchitecture.
