The Journal of Experimental Medicine
Torrey Pines Biolabs
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 1 May 2000.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 194K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Fagarasan, S.
Right arrow Articles by Honjo, T.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Fagarasan, S.
Right arrow Articles by Honjo, T.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?
© The Rockefeller University Press, 0022-1007/2000/5/1477/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 9, May 1, 2000 1477-1486

Original Article

Alymphoplasia (aly)-Type Nuclear Factor {kappa}B–Inducing Kinase (Nik) Causes Defects in Secondary Lymphoid Tissue Chemokine Receptor Signaling and Homing of Peritoneal Cells to the Gut-Associated Lymphatic Tissue System

Sidonia Fagarasana, Reiko Shinkuraa, Tadashi Kamataa, Fumiaki Nogakia, Koichi Ikutaa, Kei Tashirob, and Tasuku Honjoa

a Department of Medical Chemistry, Faculty of Medicine,
b Center for Molecular Biology and Genetics, Kyoto University, Kyoto 606-8501, Japan
Department of Medical Chemistry, Faculty of Medicine, Kyoto University, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan.81-75-753-438881-75-753-4371

honjo{at}mfour.med.kyoto-u.ac.jp

Alymphoplasia (aly) mice, which carry a point mutation in the nuclear factor {kappa}B–inducing kinase (NIK) gene, are characterized by the systemic absence of lymph nodes and Peyer's patches, disorganized splenic and thymic architectures, and immunodeficiency. Another unique feature of aly/aly mice is that their peritoneal cavity contains more B1 cells than normal and aly/+ mice. Transfer experiments of peritoneal lymphocytes from aly/aly mice into recombination activating gene (RAG)-2–/– mice revealed that B and T cells fail to migrate to other lymphoid tissues, particularly to the gut-associated lymphatic tissue system. In vivo homing defects of aly/aly peritoneal cells correlated with reduction of their in vitro chemotactic responses to secondary lymphoid tissue chemokine (SLC) and B lymphocyte chemoattractant (BLC). The migration defect of aly/aly lymphocytes was not due to a lack of expression of chemokines and their receptors, but rather to impaired signal transduction downstream of the receptors for SLC, indicating that NIK is involved in the chemokine signaling pathway known to couple only with G proteins. The results showed that the reduced serum levels of immunoglobulins (Igs) and the absence of class switch to IgA in aly/aly mice are due, at least in part, to a migration defect of lymphocytes to the proper microenvironment where B cells proliferate and differentiate into Ig-producing cells.

Key Words: RAG-2–/– mice • peritoneal cavity cell transfer • lamina propria • IgA plasma cells • chemotaxis assay

Abbreviations used in this paper: aly, alymphoplasia; BLC, B lymphocyte chemoattractant; BLR1, Burkitt's lymphoma receptor 1; BM, bone marrow; CCR, CC chemokine receptor; ELC, EBV-induced molecule 1 ligand chemokine; FDC, follicular dendritic cell; GALT, gut-associated lymphatic tissue; GAPDH, glyceraldehyde 3-phosphate dehydrogenase; GC, germinal center; LT, lymphotoxin; LP, lamina propria; MLN, mesenteric LN; NF-{kappa}B, nuclear factor {kappa}B; NIK, NF {kappa}B–inducing kinase; PEC, peritoneal cavity; PP, Peyer's patch; RAG, recombination activating gene; SLC, secondary lymphoid tissue chemokine.

© 2000 The Rockefeller University Press


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS