Figure 3. Comparison of the organogenesis programme of NALT and Peyer's patches.

CD3⁻CD4⁺CD45⁺ cells are considered to be the common inducers of secondary lymphoid tissue. ID2 (inhibitor of DNA binding 2) is indispensable for the induction and differentiation of these inducer cells from their fetal-liver precursors (which have the phenotype CD3⁻CD4⁻CD45⁺). a | For Peyer's patches, after activation through the interleukin-7 receptor (IL-7R) or TRANCE (tumour-necrosis-factor-related activation-induced cytokine), these CD3⁻CD4⁺CD45⁺ cells express the lymphotoxin-α₁β₂ (LT-α₁β₂) heterotrimer, which then binds to the LT-β receptor (LT-βR) displayed on stromal cells and induces signal transduction through NIK (nuclear factor-κB (NF-κB)-inducing kinase). In turn, NIK promotes the expression of adhesion molecules and/or chemokines. These homing molecules trigger the accumulation of lymphoid cells at the site of Peyer's patches. So, the IL-7R- and LT-βR-mediated signals are essential for the tissue genesis of Peyer's patches. b | The development of CD3⁻CD4⁺CD45⁺ cells in nasopharynx-associated lymphoid tissue (NALT) also requires ID2; however, the initiation of NALT organogenesis is independent of signalling that involves the IL-7R, LT-α₁β₂–LT-βR interactions and NIK. CCL, CC-chemokine ligand; CXCL, CXC-chemokine ligand; ICAM1, intercellular adhesion molecule 1; IKK-α, inhibitor of NF-κB (IκB) kinase-α; ROR-γ, retinoic-acid-receptor-related orphan receptor-γ; VCAM1, vascular cell-adhesion molecule 1.