In order to definitively ascertain the functional contribution of lymphotoxin (LT) expressed by B cells, we produced mice with the LTβ gene deleted from B cells (B-LTβ KO mice). In contrast to systemic LTβ deletion, in B-LTβ KO mice only splenic microarchitecture was affected, while lymph nodes and Peyer's patches (PP) were normal, except for PP's reduced size. Even though B-LTβ KO spleens retained a small number of follicular dendritic cells (FDC) which appeared to be dependent on LTβ produced by T cells, IgG responses to sheep red blood cells were markedly reduced. Thus, the organogenic function of B-LTβ is almost entirely restricted to spleen, where it supports the correct lymphoid architecture that is critical for an effective humoral immune response.