TNF and lymphotoxin beta 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 alpha (lt alpha)- and all lymphotoxin beta receptor (lt beta)-deficient mice are completely devoid of lymph nodes (LNs); however, most lymphotoxin beta (lt beta)-deficient mice develop mesenteric LNs, Tnf- and tnfrp55-deficient mice develop a complete set of LNs, while lt beta/tnfrp55 double-deficient mice lack all LNs, demonstrating cooperation between LT beta and TNFRp55 in LN development. Now we report that lt beta/tnf double-deficient mice develop the same set of mucosal LNs as do lt beta-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 lt beta-deficient mice but not in lt beta/tnf double-deficient mice. Additionally, stromal components of the spleen and LNs appear to be more severely disturbed in lt beta/tnf double-deficient mice as compared with lt beta-deficient mice. We conclude that LT beta and TNF cooperate in the establishment of the correct microarchitecture of lymphoid organs. [References: 45]

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