Regulation of T(H)2 development by CXCR5(+) dendritic cells and lymphotoxin-expressing B cells

Although cognate encounters between CCR7-expressing antigen-bearing dendritic cells (DCs) and CCR7(+) naïve T cells take place within the T cell zone of lymph nodes, it is unknown whether co-localization of the DCs and T cells within the T cell area is obligate for effector generation. Here, we show that, following nematode infection, antigen-bearing DCs and CD4(+) T cells upregulate CXCR5 and co-localize in a CXCL13, B cell and lymphotoxin-dependent fashion outside of the T zone. Importantly, lymphotoxin-expressing B cells, CXCL13 and CXCR5-expressing DCs and T cells are also necessary for development of interleukin 4 (IL-4) producing T(H)2 cells, suggesting that T(H)2 differentiation can initiate outside of the T cell zone.