Postgestational lymphotoxin/lymphotoxin beta receptor interactions are essential for the presence of intestinal B lymphocytes.
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 LTbetaR is essential for the presence LP B lymphocytes. The LT/LTbetaR-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/LTbetaR. The LT-dependent signal relevant for the presence of LP B lymphocytes is optimally supplied by a LT-sufficient B lymphocyte, and requires a LTbetaR-sufficient radio-resistant, non-bone marrow-derived cell. Based upon the severity of the deficit of LP B lymphocytes we observed, these novel LT/LTbetaR-dependent events are of primary importance in directing the entry and residence of LP B lymphocytes.
Newberry
Rodney D
RD
Division of Gastroenterology, Department of Internal Medicine, Washington University School of Medicine, 660 S. Euclid Avenue, St. Louis, MO 63110, USA.
McDonough
Jacquelyn S
JS
McDonald
Keely G
KG
Lorenz
Robin G
RG
D000818:Animals; D016175:B-Lymphocyte Subsets / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000528:radiation effects; D001854:Bone Marrow Cells / Q000276:immunology; D005260:Female; D005720:Gamma Rays; D007413:Intestinal Mucosa / Q000166:cytology / Q000276:immunology* / Q000378:metabolism* / Q000528:radiation effects; D016131:Lymphocyte Subsets / Q000166:cytology / Q000276:immunology / Q000378:metabolism / Q000528:radiation effects; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha / Q000378:metabolism* / Q000502:physiology*; D053308:Lymphotoxin-beta; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D049590:Postpartum Period / Q000276:immunology*; D011247:Pregnancy; D011828:Radiation Chimera / Q000276:immunology; D011836:Radiation Tolerance / Q000276:immunology; D018124:Receptors, Tumor Necrosis Factor / Q000502:physiology* / Q000528:radiation effects; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
C505887:Ltb protein, mouse; C505699:Ltbr protein, mouse; D053259:Lymphotoxin beta Receptor; D008233:Lymphotoxin-alpha; D053308:Lymphotoxin-beta; D008565:Membrane Proteins; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha