Schematic choreography of cells and molecules in ATLO neogenesis. Blood monocytes/macrophages/foam cells, T cells, and SMCs form atherosclerotic lesions in the intima and initiate a transmural arterial wall inflammation pathway. Lesion cells such as CD11c⁺ and/or CD11c⁻ myeloid cells and T cells produce TNFR agonists LTβ and TNF and, after LTβR/TNFRSF1A activation and induction of alternative and classical NF-κB signaling pathways, media SMCs are activated and acquire features of lymphoid tissue organizers. Lymphorganogenic CXCL13/CCL21 and other mediators gain access to cells residing in the adventitia, recruit B and T cells through vasa vasora, and promote lymphocyte and stromal cell activation. A tissue microenvironment is then generated that induces conduit neogenesis via stimulation of reticular fibroblasts, DC recruitment, HEV formation, ectopic lymph vessel, and blood vessel neogenesis. ATLO formation accelerates and lymphocyte recirculation is markedly facilitated, B cell follicles form, and T reg cells in T cell areas are recruited. Transmural inflammation also generates autoantigen(s), although their nature, transport routes, and functional roles all remain to be defined. Accelerated B cell recruitment leads to B cell follicle formation, and ectopic GCs are activated. Autoantigen-binding FDCs initiates B cell proliferation, differentiation, and affinity maturation. Memory cells and/or plasma cells, and possibly autoreactive T/B cells, together with T reg cell deficiency may lead to clinically apparent and overt autoimmunity and arterial wall pathology.