TNF and lymphotoxin β cooperate in the maintenance of secondary lymphoid tissue microarchitecture but not in the development of lymph nodes

Inactivation of genes encoding members of TNF and TNF receptor families reveal their divergent roles in the formation and function of secondary lymphoid organs. Most lymphotoxin α (ltα)- and all lymphotoxin β receptor (ltβr)-deficient mice are completely devoid of lymph nodes (LNs); however, most lymphotoxin β (ltβ)-deficient mice develop mesenteric LNs. Tnf- and tnfrp55-deficient mice develop a complete set of LNs, while ltβ/tnfrp55 double-deficient mice lack all LNs, demonstrating cooperation between LTβ and TNFRp55 in LN development. Now we report that ltβ/tnf double-deficient mice develop the same set of mucosal LNs as do ltβ-deficient mice, suggesting that ligands other than TNF signal through TNFRp55 during LN development. These LNs retain distinct T and B cells areas; however, they lack follicular dendritic cell networks. Structures resembling germinal centers can be found in the LNs from immunized ltβ-deficient mice but not in ltβ/tnf double-deficient mice. Additionally, stromal components of the spleen and LNs appear to be more severely disturbed in ltβ/tnf double- deficient mice as compared with ltβ-deficient mice. We conclude that LTβ and TNF cooperate in the establishment of the correct microarchitecture of lymphoid organs.