Lymph node development Flashcards
What is the hallmark feature of secondary lymph organs?
Highly ordered compartmentalization of T and B cells and also myeloid cells.
What is the role of (non-hematopoietic) lymph node stromal cells?
Maintain LN integrity and function, play a role in organogenesis and support immune responses.
What two cells types lead to LN organogenesis in humans and around what weeks?
Lymphoid Tissue Inducer (LTi) and Lymphoid Tissue organizer (LTo) around weeks 8 to 11 of gestation
LTi cells have a CD45 marker. What does that mean?
They are hematopoietic stem cells.
What two transcription factors lead to the formation of LTi cells?
Id2 and RORyt.
What are CXCR5 and CCR7?
Chemokine receptors.
Do LTo cells have a CD45 marker? What does that mean?
They do not, LTo are non-hematopoietic / non-stem cells.
What chemokines bind to CCR7?
CCL19 and CCL21
How do LTi cells induce LTo cells?
LTi cells produce lymphotoxin, which binds to LTbR on LTo.
What chemokines does CXCR5 bind?
CXCL13
What do CXCR5 or CXCL13 deficient mice develop?
They lack most LNs
What do CCR7 or CCL19/21 deficient mice develop?
Develop all LNs, but they are smaller and badly organized.
Briefly describe the steps of LN development.
LTi cells are found in the fetal liver. They travel to spots called “LN Anlagen” which are line ‘nests’ where Lymph Nodes will develop. LTi cells that travel to those nests start recruiting LTo cells that are of mesenchymal (mLTo) or endothelial origin (eLTo). LTo cells then create a feed-forward loop that recruits more LTi cells.
Which molecule and where is suggested to play a role in setting up the LN Anlage?
Lymphotoxin (LT) signaling in mesenchymal cells has been found to potentially play a role in the anlage development.
What is the role of High Endothelial Venules (HEV)?
Those are cuboidal cells at the differentiated end of the lymph node venule, which play a role in catching lymphatic cells and transporting them into the LN.
What signaling molecules do HEVs need to transport cells to the LN?
They need LTbR signaling by LT from DC.
What are the three compartments of the lymph node and what ells does it harbor?
- Cortex - the outer part of the LN and harbors B-cells within individual B-cell follicles.
- Paracortex - beneath the cortex in which T-cells and DCs are located
- Medulla - The basal part of the LN, is where macrophages and plasma cells are found. They also contain sinuses to facilitate lymph flow.
What type of cells is important for the migration of specific cells to specific places WITHIN the lymph node?
The Fibroblastic Reticular Cells (FRC).
What is PDPN a marker of?
FRC
Briefly explain FRC development.
Development of FRC starts when mesenchymal LTo cells transition to the precursor cells in an LT-independent manner. Then The formation of FRC from the precursor requires LT / LTbR signaling.
What is CLEC2 important for?
FRCs and LECs both express PDPN in order to bind to CLEC2 on DC. This is important for the transport of DC into the lymph node.
Aka. Important for DC transport into LN.
Where are TRCs located, what do they secrete and why?
TRCs are found in the T-cell zones of the LN. They secrete homeostatic CCL19 and CCL21 and mediate the recruitment of CCR7 naive T-cells and DCs to facilitate their interactions.
How is a chemokine gradient established in the LN and what is it used for?
LECs (border of the LN) produce a chemokine used in degradation, so once cells enter the LN, they will travel to the highest concentration of their respective chemokine, which will be higher the further away it is from the border of the LN.
What happens during loss of LT and TNF?
FDC (FRC for DC) do not develop properly.
