Abnormal Development of Secondary Lymphoid Tissues in Lymphotoxin Beta-Deficient Mice

The tumor necrosis factor (TNF) family cytokines lymphotoxin (LT) alpha and LT beta form heterotrimers that are expressed on the surface of activated lymphocytes and natural killer cells; LT alpha homotrimers can be secreted as well, Mice with a disrupted LT alpha gene lack lymph nodes (LN), Fever's patches (PP), and follicular dendritic cell (FDC) networks and reveal profound defects of the splenic architecture, However, it is unclear which of these abnormalities is the result of the absence in LT alpha homotrimers or LT alpha beta heterotrimers. To distinguish between these two possibilities, a mouse strain deficient in LT beta was created employing Cre/loxP-mediated gene targeting, Mice deficient in LT beta reveal severe defects in organogenesis of the lymphoid system similar to those of LT alpha(-/-)mice, except that mesenteric and cervical LN are present in most LT beta-deficient mice, Both LT alpha- and LT alpha-deficient mice show significant lymphocytosis in the circulation and peritoneal cavity and lymphocytic infiltrations in lungs and liver. After immunization, PNA-positive B cell clusters were detected in the splenic white pulp of LT beta-deficient mice, but FDC networks were severely underdeveloped, Collectively, these results indicate that LT alpha can signal independently from LT beta in the formation of PNA-positive foci in the spleen, and especially in the development of mesenteric and cervical LN. [References: 43]

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