B lymphocytes deliver lymphotoxin-dependent signals for the development of follicular dendritic cell clusters

Lymphotoxin (LT) signals the induction of peripheral lymphoid tissue structures. In the spleen, LT supports the development of the white pulp. In LTα-deficient (LTα^-/-) mice, spleen follicular dendritic cell (FDC) clusters and germinal centers (GC) do not form. This is accompanied by inability to develop high affinity IgG responses following immunization with T-dependent antigens. Transfer of bone marrow (BM) from wild-type mice to LTα^-/- recipients restores FDC clusters and the ability to produce high affinity IgG antibodies, whereas transfer of BM from LTα^-/- mice to lethally irradiated wild-type mice results in the loss of FDC clusters and IgG responses. Thus, FDC/GC structures are important for the maturation of B cell responses and LTα-expressing BM-derived cells are required for the formation of FDC clusters. Furthermore, the LTα signal provided by these cells supports both the induction and the maintenance of normal FDC structure. To determine the cell lineage required to deliver the LTα-dependent signal for FDC formation, we analyzed the spleen structures of T cell-deficient and B cell-deficient mouse strains. LTα-expressing B cells alone were essential and sufficient to signal the formation of FDC clusters. Once these clusters were induced by LTα-expressing B cells, then LTα-deficient T cells could interact with B cells to generate GC and productive class switched antibody responses. Thus, B cells themselves provide an essential signal that induces and maintains the lymphoid microenvironment essential for GC formation and class switched Ig responses.