Abstract
The gastrointestinal mucosa contains a complex network of lymphoid compartments that have evolved to efficiently protect the host from invading pathogens. Recently, an additional lymphoid structure resembling Peyer's patches (PP) in composition and architecture has been identified in the murine small intestine, the isolated lymphoid follicle (ILF). In this study we examine the nature and factors required for ILF formation. We observed a spectrum of structures fitting the previous descriptions of ILFs, ranging from clusters of B220(+) cells (which we have termed immature ILFs) to well-organized lymphoid nodules (which we have termed mature ILFs). Here we demonstrate that that similar to PP formation, ILF formation requires lymphotoxin (LT)- and LT beta receptor-dependent events. However unlike PP formation, the LT- and LT beta receptor-dependent events required for ILF formation can occur in adulthood and require LT-sufficient B lymphocytes. We demonstrate that mature ILF formation occurs in response to lumenal stimuli, including normal bacterial flora, and requires TNF receptor I function. These findings suggest that ILFs are organized intestinal lymphoid structures whose formation can be induced and whose mass can be expanded in response to mucosal challenges.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Aging / genetics
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Aging / immunology
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Animals
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Antigens, CD / genetics
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Antigens, CD / physiology*
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B-Lymphocyte Subsets / cytology
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B-Lymphocyte Subsets / immunology*
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B-Lymphocyte Subsets / metabolism*
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Cell Aggregation / genetics
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Cell Aggregation / immunology
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Cell Differentiation / genetics
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Cell Differentiation / immunology
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Female
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Intestinal Mucosa / growth & development
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Intestinal Mucosa / immunology
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Intestinal Mucosa / metabolism
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Intestinal Mucosa / microbiology
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Intestine, Small / growth & development
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Intestine, Small / immunology
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Intestine, Small / metabolism
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Intestine, Small / microbiology
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Leukocyte Common Antigens / biosynthesis
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Lymphoid Tissue / growth & development*
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Lymphoid Tissue / immunology*
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Lymphoid Tissue / metabolism
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Lymphoid Tissue / microbiology
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Lymphotoxin beta Receptor
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Lymphotoxin-alpha / biosynthesis
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Lymphotoxin-alpha / deficiency
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Lymphotoxin-alpha / metabolism
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Lymphotoxin-alpha / physiology*
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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Pregnancy
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Receptors, Tumor Necrosis Factor / biosynthesis
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Receptors, Tumor Necrosis Factor / deficiency
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Receptors, Tumor Necrosis Factor / genetics
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Receptors, Tumor Necrosis Factor / physiology*
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Receptors, Tumor Necrosis Factor, Type I
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Stromal Cells / immunology
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Stromal Cells / metabolism
Substances
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Antigens, CD
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Ltbr protein, mouse
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Lymphotoxin beta Receptor
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Lymphotoxin-alpha
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Receptors, Tumor Necrosis Factor
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Receptors, Tumor Necrosis Factor, Type I
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Leukocyte Common Antigens