Abstract
High levels of the Rel/NF-kappaB family member RelB are restricted to specific regions of thymus, lymph nodes, and Peyer's patches. In spleen, RelB is expressed in periarteriolar lymphatic sheaths, germinal centers (GCs), and the marginal zone (MZ). In this study, we report that RelB-deficient (relB(-/-)) mice, in contrast to nfkb1(-/-), but similar to nfkb2(-/-) mice, are unable to form GCs and follicular dendritic cell networks upon Ag challenge in the spleen. RelB is also required for normal organization of the MZ and its population by macrophages and B cells. Reciprocal bone marrow transfers demonstrate that RelB expression in radiation-resistant stromal cells, but not in bone marrow-derived hemopoietic cells, is required for proper formation of GCs, follicular dendritic cell networks, and MZ structures. However, the generation of MZ B cells requires RelB in hemopoietic cells. Expression of TNF ligand/receptor family members is only moderately altered in relB(-/-) splenocytes. In contrast, expression of homing chemokines is strongly reduced in relB(-/-) spleen with particularly low mRNA levels of the chemokine B lymphocyte chemoattractant. Our data indicate that activation of p52-RelB heterodimers in stromal cells downstream of TNF/lymphotoxin is required for normal expression of homing chemokines and proper development of spleen microarchitecture.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Antigen-Antibody Complex / metabolism
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B-Lymphocytes / immunology
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B-Lymphocytes / pathology
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Cell Movement / genetics
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Cell Movement / immunology*
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Chemokines, CC / biosynthesis*
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Dendritic Cells, Follicular / immunology
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Dendritic Cells, Follicular / pathology
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Germinal Center / metabolism*
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Germinal Center / pathology*
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Germinal Center / radiation effects
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Immunohistochemistry
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Lymphopenia / genetics
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Lymphopenia / immunology
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Lymphotoxin beta Receptor
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Macrophages / immunology
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Macrophages / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Knockout
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NF-kappa B / antagonists & inhibitors
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NF-kappa B / genetics
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Proto-Oncogene Proteins / biosynthesis
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Proto-Oncogene Proteins / deficiency
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Proto-Oncogene Proteins / genetics
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Proto-Oncogene Proteins / physiology*
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Radiation Chimera / immunology
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Receptors, Tumor Necrosis Factor / biosynthesis
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Spleen / metabolism*
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Spleen / pathology*
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Spleen / radiation effects
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Stromal Cells / immunology
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Stromal Cells / pathology
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Transcription Factor RelB
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Transcription Factors / biosynthesis
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Transcription Factors / deficiency
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Transcription Factors / genetics
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Transcription Factors / physiology*
Substances
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Antigen-Antibody Complex
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Chemokines, CC
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Ltbr protein, mouse
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Lymphotoxin beta Receptor
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NF-kappa B
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Proto-Oncogene Proteins
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Receptors, Tumor Necrosis Factor
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Relb protein, mouse
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Transcription Factors
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Transcription Factor RelB