Mesenchymal cell differentiation during lymph node organogenesis

Abstract

Secondary lymphoid tissues such as lymph nodes are essential for the interactions between antigen presenting cells and lymphocytes that result in adaptive immune responses that protect the host against invading pathogens. The specialized architecture of these organs facilitates the cognate interactions between antigen-loaded dendritic cells and lymphocytes expressing their specific receptor as well as B-T cell interactions that are at the core of long lasting adaptive immune responses. Lymph nodes develop during embryogenesis as a result of a series of cross-talk interactions between a hematopoietically derived cell lineage called lymphoid tissue inducer cells and stromal cells of mesenchymal origin to form the anlagen of these organs. This review will present an overview of the different signaling pathways and maturation steps that mesenchymal cells undergo during the process of lymph node formation such as cell specification, priming, and maturation to become lymphoid tissue stromal organizer cells.

Keywords: NF-κB; lympho-mesenchymal interactions; lymphoid tissues; lymphotoxin beta receptor; stromal cells.

FIGURE 1

Model of lymph node development. Step 1: Retinoic Acid produced by neurons stimulates mesenchymal cells to express the chemokine CXCL13. Step 2: CXCL13 expression by mesenchymal cells attracts lymphoid tissue inducer (LTi) cells to the site where lymph nodes will develop. LTi cells will cluster and they might signal in trans to each other through RANKL-RANK. Step 3: RANK signaling on LTi cells will induce high expression levels of LTα1β2. Binding of the latter to LTβR on mesenchymal cells will induce the expression of cell adhesion molecules VCAM-1, ICAM-1, and MAdCAM-1 as well as CXCL13, CCL21, and CCL19 to initiate a positive feedback loop that will attract large numbers of LTi cells to the LN anlage and thus result in the formation of the structure the organs.