title: Abnormal organogenesis of Peyer's patches in mice deficient for NF-kappaB1, NF-kappaB2, and Bcl-3.
abstract: OBJECTIVE
  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 PP in NF-kappaB2(-/-) mice. Whole-mount in situ hybridization revealed the presence of interleukin-7 receptor-alpha 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.
authors.affiliation: Department of Internal Medicine I, Ulm University, Ulm, Germany.
authors.forename: Stephan
authors.initials: S
authors.lastname: Paxian
authors.forename: Heidrun
authors.initials: H
authors.lastname: Merkle
authors.forename: Marc
authors.initials: M
authors.lastname: Riemann
authors.forename: Monika
authors.initials: M
authors.lastname: Wilda
authors.forename: Guido
authors.initials: G
authors.lastname: Adler
authors.forename: Horst
authors.initials: H
authors.lastname: Hameister
authors.forename: Susanne
authors.initials: S
authors.lastname: Liptay
authors.forename: Klaus
authors.initials: K
authors.lastname: Pfeffer
authors.forename: Roland M
authors.initials: RM
authors.lastname: Schmid
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000081242:B-Cell Lymphoma 3 Protein; D015815:Cell Adhesion Molecules; D054418:Chemokine CCL20; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC / Q000378:metabolism; D003713:Dendritic Cells / Q000145:classification / Q000502:physiology; D015870:Gene Expression; D018858:Germinal Center / Q000502:physiology; D007136:Immunoglobulins / Q000378:metabolism; D008214:Lymphocytes / Q000378:metabolism / Q000473:pathology; D019402:Macrophage Inflammatory Proteins; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D009088:Mucoproteins / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D016328:NF-kappa B / Q000235:genetics / Q000502:physiology*; D052003:NF-kappa B p52 Subunit; D010581:Peyer's Patches / Q000254:growth & development* / Q000473:pathology; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000502:physiology*; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000081242:B-Cell Lymphoma 3 Protein; C000631344:BCL3 protein, human; C000631345:Bcl3 protein, mouse; C108355:CCL20 protein, human; C106311:CCR6 protein, human; D015815:Cell Adhesion Molecules; D054418:Chemokine CCL20; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; C486386:Cxcl13 protein, mouse; D007136:Immunoglobulins; C504265:MADCAM1 protein, human; D019402:Macrophage Inflammatory Proteins; C489082:Madcam1 protein, mouse; D009088:Mucoproteins; D016328:NF-kappa B; D052003:NF-kappa B p52 Subunit; C504649:PSIP1 protein, human; D011518:Proto-Oncogene Proteins; C504650:Psip1 protein, mouse; D054399:Receptors, CCR6; D019707:Receptors, Chemokine; D015534:Trans-Activators; D014157:Transcription Factors