Lymphotoxin-alpha-deficient and TNF receptor-I-deficient mice define developmental and functional characteristics of germinal centers

Immunological Reviews
M MatsumotoD D Chaplin

Abstract

Mice deficient in LT alpha (LT alpha-/-) lack lymph nodes and Peyer's patches. This action of LT alpha in lymph node organogenesis appears to be mediated by the membrane form of LT using a mechanism independent of TNF receptor I (TNFR-I) or II (TNFR-II). In contrast, normal Peyer's patch development appears to require both LT alpha and TNFR-I, with TNFR-I-/- mice showing hypoplastic Peyer's patch structures. LT alpha-/- mice also fail to support the normal segregation of T-cell and B-cell zones within the splenic white pulp. Again, this occurs via a mechanism independent of TNFR-I or TNFR-II. Additionally, follicular dendritic cell (FDC) clusters or germinal centers fail to develop in the spleen of LT alpha-/- animals. Mice deficient in either TNF alpha or TNFR-I also fail to develop splenic FDC clusters and germinal centers, indicating that signaling by both LT alpha and TNF alpha is required for development of these specialized lymphoid tissue structures. Finally, the splenic white pulp areas in LT alpha-/- mice lack the marginal zone of monoclonal antibody MOMA-1-staining metallophilic macrophages, whereas TNFR-I-deficient mice have preserved MOMA-1 staining. Thus, certain actions of LT alpha to regulate spleen white pulp ar...Continue Reading

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