A putative model for role of LTis in innate and adaptive immunity. FDC, follicular dendritic cell, DC, dendritic cell, B, B cell, T, T cell, LTi, lymphoid tissue inducer cell. (a) Putative LTi-like cells, present within the primitive immune system of the gut, promote epithelial integrity at mucosal surfaces through secretion of IL22. (b) LTi, adapted through expression of the lymphotoxin genes, orchestrate the organization of B cells and CD11c+ DCs into isolated lymphoid follicles (ILFs). These foster T-independent (TI) IgA class-switched plasma cells, mediated by BAFF and APRIL (expressed by DC), again to promote mucosal integrity. (c) Evolution of CD40-dependent T-cell selection within ILFs. LTis acquire the new TNF ligands (CD30L and OX40L), which evolve to promote CD4 memory.69 (d) Classical T-dependent (TD) responses in lymph node and spleen. In B follicles, CD40L-expressing CD4 T cells, LTis, and FDCs foster activation-induced cytidine deaminase (AID)-dependent affinity maturation in germinal center (GC). In the outer T-zone, T (CD40L) and CD11c+ cells (BAFF and APRIL) foster AID-dependent class switching in B cells that become plasma cells.