A stroma-derived defect in NF-kappaB2-/- mice causes impaired lymph node development and lymphocyte recruitment.
The NF-kappaB family of transcription factors is vital to all aspects of immune function and regulation in both the hemopoietic and stromal compartments of immune environments. Recent studies of mouse models deficient for specific members of the NF-kappaB family have revealed critical roles for these proteins in the process of secondary lymphoid tissue organogenesis. In this study, we investigate the role of NF-kappaB family member NF-kappaB2 in lymph node development and lymphocyte recruitment. Inguinal lymph nodes in nfkappab2(-/-) mice are reduced in size and cellularity, most notably in the B cell compartment. Using in vitro and in vivo lymph node grafting assays, we show that the defect resides in the stromal compartment. Further examination of the nfkappab2(-/-) inguinal lymph nodes revealed that expression of peripheral node addressin components CD34 and glycosylation-dependent cell adhesion molecule-1 along with the high endothelial venule-restricted sulfotransferase HEC-GlcNAc6ST was markedly reduced. Furthermore, expression of the lymphocyte homing chemokines CCL19, CCL21, and CXCL13 was down-regulated. These data highlight the role of NF-kappaB2 in inguinal lymph node organogenesis and recruitment of lymphocytes to these organs due to its role in up-regulation of essential cell adhesion molecules and chemokines, while suggesting a potential role for NF-kappaB2 in organization of lymph node endothelium.
Department of Anatomy, Medical Research Council Centre for Immune Regulation, The Medical School, University of Birmingham, Edgbaston, United Kingdom.
Damian
D
Carragher
Ramneek
R
Johal
Adele
A
Button
Andrea
A
White
Aristides
A
Eliopoulos
Eric
E
Jenkinson
Graham
G
Anderson
Jorge
J
Caamaño
D000818:Animals; D018952:Antigens, CD34 / Q000096:biosynthesis / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC / Q000276:immunology / Q000378:metabolism; D019743:Chemokines, CXC / Q000276:immunology / Q000378:metabolism; D005434:Flow Cytometry; D008198:Lymph Nodes / Q000166:cytology* / Q000254:growth & development* / Q000276:immunology; D008214:Lymphocytes / Q000166:cytology* / Q000276:immunology; D051379:Mice; D018448:Models, Immunological; D009077:Mucins / Q000096:biosynthesis / Q000276:immunology; D016328:NF-kappa B / Q000172:deficiency / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000276:immunology; D017154:Stromal Cells / Q000276:immunology*; D015238:Sulfotransferases / Q000096:biosynthesis / Q000276:immunology; D000097811:Carbohydrate Sulfotransferases
D018952:Antigens, CD34; D054415:Chemokine CCL19; D054421:Chemokine CCL21; D054382:Chemokine CXCL13; D019742:Chemokines, CC; D019743:Chemokines, CXC; D009077:Mucins; D016328:NF-kappa B; D015238:Sulfotransferases; D000097811:Carbohydrate Sulfotransferases; C515461:Ccl19 protein, mouse; C515479:Ccl21c protein, mouse; C486386:Cxcl13 protein, mouse; C075185:sulfated glycoprotein p50