TY - JOUR
T1 - A stroma-derived defect in NF-κB2-/- mice causes impaired lymph node development and lymphocyte recruitment
AU - Carragher, Damian
AU - Johal, Ramneek
AU - Button, Adele
AU - White, Andrea
AU - Eliopoulos, Aristides
AU - Jenkinson, Eric
AU - Anderson, Graham
AU - Caamaño, Jorge
PY - 2004/8/15
Y1 - 2004/8/15
N2 - The NF-κB 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-κB 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-κB family member NF-κB2 in lymph node development and lymphocyte recruitment. Inguinal lymph nodes in nfκb2-/- 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 nfκb2-/- 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-κB2 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-κB2 in organization of lymph node endothelium.
AB - The NF-κB 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-κB 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-κB family member NF-κB2 in lymph node development and lymphocyte recruitment. Inguinal lymph nodes in nfκb2-/- 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 nfκb2-/- 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-κB2 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-κB2 in organization of lymph node endothelium.
UR - http://www.scopus.com/inward/record.url?scp=4043129589&partnerID=8YFLogxK
U2 - 10.4049/jimmunol.173.4.2271
DO - 10.4049/jimmunol.173.4.2271
M3 - Article
C2 - 15294939
AN - SCOPUS:4043129589
SN - 0022-1767
VL - 173
SP - 2271
EP - 2279
JO - Journal of Immunology
JF - Journal of Immunology
IS - 4
ER -