Lymphoid organ specificity in the maintenance of secondary lymphoid tissues by TNF produced by B and T cells (95.26)

Abstract

Abstract Secondary lymphoid organs play an important role in generation of efficient immune responses. Using a genetic approach we revealed distinct contribution of TNF produced by B and T cells in homeostasis of secondary lymphoid organs. In spleen, the development of follicular dendritic cells (FDC) and B cell follicles was controlled primarily by TNF produced by B cells while TNF from T cells provided a distinct complementary signal, similarly to contributions reported earlier for the surface lymphotoxin (LT). Organized marginal zone structure was dependent on TNF from both B-, T- and other cell types. In contrast, in Peyer’s patches, the lymphoid microarchitecture was exclusively dependent on TNF produced by B cells. Furthermore, we show that TNF signals from both B and T cells acted in concert for the expression of TNF dependent genes in lymph nodes, generation of FDC and B cell follicles, and in mounting an efficient humoral immune response to thymus-dependent antigen. Finally, we found that soluble form of TNF provided by B cells was critical for the maintenance of secondary lymphoid organs. Thus, the organization of different secondary lymphoid organs is maintained by distinct contribution of TNF produced by B and T cells, on one hand, and distinct role of soluble versus membrane TNF form, on the other hand.