Abnormal organogenesis of Peyer's patches in mice deficient for NF-κB1, NF-κB2, and Bcl-3

被引:53
作者
Paxian, S
Merkle, H
Riemann, M
Wilda, M
Adler, G
Hameister, H
Liptay, S
Pfeffer, K
Schmid, RM
机构
[1] Univ Ulm, Dept Internal Med, D-89081 Ulm, Germany
[2] Univ Ulm, Dept Med Genet, D-89081 Ulm, Germany
[3] Univ Ulm, Dept Pediat, D-89081 Ulm, Germany
[4] Tech Univ Munich, Inst Microbiol & Hyg, D-8000 Munich, Germany
关键词
D O I
10.1053/gast.2002.33651
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
Background & Aims: Nuclear factor (NF) kappaB1, NF-kappaB2, and Bcl-3 encode for proteins of the NF-kappaB/Rel/IkappaB families, known as regulators of innate and adoptive immune responses. Targeted disruption of these genes showed essential roles in lymphoid organ development and organization. Methods: NF-kappaB1-, NF-kappaB2-, and Bcl-3-deficient mouse lines were established, and their role in organogenesis of Peyer's patches (PP) was investigated. Results: Macroscopic inspection showed a reduced number and size of PP in Bcl-3(-/-) and NF-kappaB1(-/-) mice but failed to detect PIP in NF-kappaB2(-/-) mice. Wholemount in situ hybridization revealed the presence of interleukin-7 receptor-sigma spots in NF-kappaB2(-/-) mice, indicating no defect in PP organogenesis of NF-kappaB2(-/-) mice in principle. Immunostaining shows that residual lymphocytes mainly consist of T cells. B cells are substantially reduced and are accumulated as terminal extravasations. Organized follicular structures and follicular dendritic cell networks fail to form, and myeloid, but not lymphoid, dendritic cells are obviously reduced. Expression of the chemokines macrophage inflammatory protein-3alpha, B-lymphocyte chemoattractant, and thymus-expressed chemokine is impaired in epithelial cells and in the subendothelial dome area that is not well defined. A similar but less severe phenotype is seen in Bcl-3(-/-) mice, which also do not develop germinal centers. In contrast, in NF-kappaB1(-/-) mice, T-cell numbers are visibly reduced, and no alteration could be observed in the B-cell and dendritic-cell populations. Conclusions: These data show that all 3 genes are crucial for PP development but contribute differently to PP organogenesis.
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页码:1853 / 1868
页数:16
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