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The Journal of Immunology, 2002, 168: 4988-4997.
Copyright © 2002 by The American Association of Immunologists

Postgestational Lymphotoxin/Lymphotoxin {beta} Receptor Interactions Are Essential for the Presence of Intestinal B Lymphocytes1

Rodney D. Newberry*,{dagger}, Jacquelyn S. McDonough{ddagger}, Keely G. McDonald*,{dagger} and Robin G. Lorenz2,{dagger},{ddagger}

* Division of Gastroenterology, Departments of {dagger} Internal Medicine, and {ddagger} Pathology and Immunology, Washington University School of Medicine, St. Louis, MO 63110

Lymphotoxin (LT), a cytokine belonging to the TNF family, has established roles in the formation of secondary lymphoid structures and in the compartmentalization of T and B lymphocyte areas of the spleen. In this study, we examine the role of LT in directing the composition of intestinal lymphocytes. We report that mice deficient in LT have a normal composition of intestinal lamina propria (LP) T lymphocytes, and an absence of intestinal LP B lymphocytes. We further refine this observation to demonstrate that the interaction of LT with the LT{beta}R is essential for the presence LP B lymphocytes. The LT/LT{beta}R-dependent events relevant for the presence of LP B lymphocytes occur after birth, do not require the presence of Peyer’s patches, lymph nodes, or the spleen; and therefore, are distinct and independent from the previously identified roles of LT/LT{beta}R. The LT-dependent signal relevant for the presence of LP B lymphocytes is optimally supplied by a LT-sufficient B lymphocyte, and requires a LT{beta}R-sufficient radio-resistant, non-bone marrow-derived cell. Based upon the severity of the deficit of LP B lymphocytes we observed, these novel LT/LT{beta}R-dependent events are of primary importance in directing the entry and residence of LP B lymphocytes.




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