Abnormal Development of Secondary Lymphoid Tissues in Lymphotoxin β -deficient Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 94; no. 17; pp. 9302 - 9307
• Main Authors: Alimzhanov, Marat B., Kuprash, Dmitry V., Kosco-Vilbois, Marie H., Luz, Arne, Turetskaya, Regina L., Tarakhovsky, Alexander, Rajewsky, Klaus, Nedospasov, Sergei A., Pfeffer, Klaus
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences of the United States of America 19-08-1997; National Acad Sciences; National Academy of Sciences; The National Academy of Sciences of the USA
• Subjects: Animals; B lymphocytes; Biological Sciences; Cellular biology; Follicular dendritic cells; Gene Expression Regulation, Developmental - immunology; Immunity (Disease); Lymph nodes; Lymphatic system; Lymphocytes; Lymphoid tissue; Lymphoid Tissue - immunology; Lymphoid Tissue - pathology; Lymphotoxin-alpha - genetics; Lymphotoxin-alpha - immunology; Lymphotoxin-beta; Membrane Proteins - genetics; Membrane Proteins - immunology; Mice; Mice, Knockout; Pharmacology; Receptors; Rodents; Signal Transduction - immunology; Spleen; T lymphocytes; Tumor Necrosis Factor-alpha - genetics; Tumor Necrosis Factor-alpha - immunology; Tumor necrosis factors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.94.17.9302

The tumor necrosis factor (TNF) family cytokines lymphotoxin (LT) α and LTβ form heterotrimers that are expressed on the surface of activated lymphocytes and natural killer cells; LTα homotrimers can be secreted as well. Mice with a disrupted LTα gene lack lymph nodes (LN), Peyer'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 LTα homotrimers or LTα β heterotrimers. To distinguish between these two possibilities, a mouse strain deficient in LTβ was created employing Cre/loxP-mediated gene targeting. Mice deficient in LTβ reveal severe defects in organogenesis of the lymphoid system similar to those of LTα-/-mice, except that mesenteric and cervical LN are present in most LTβ -deficient mice. Both LTβ - and LTα -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 LTβ -deficient mice, but FDC networks were severely underdeveloped. Collectively, these results indicate that LTα can signal independently from LTβ in the formation of PNA-positive foci in the spleen, and especially in the development of mesenteric and cervical LN.