The Journal of Experimental Medicine
Keystone Symposia 2010 Conferences
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 235K)
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 Kopf, M.
Right arrow Articles by Kosco-Vilbois, M. H.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Kopf, M.
Right arrow Articles by Kosco-Vilbois, M. H.
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, 0022-1007/1998/11/1895/ $5.00
The Journal of Experimental Medicine, Volume 188, Number 10, November 16, 1998 1895-1906

Articles

Interleukin 6 Influences Germinal Center Development and Antibody Production via a Contribution of C3 Complement Component

Manfred Kopf*, Suzanne Herren{ddagger}, Michael V. Wiles§, Mark B. Pepys||, and Marie H. Kosco-Vilbois{ddagger}

From the * Basel Institute for Immunology, CH-4005 Basel, Switzerland; {ddagger} Geneva Biomedical Research Institute, Glaxo Wellcome Research and Development, CH-1228 Geneva, Switzerland; § Max-Planck Institute for Molecular Genetics, Berlin, D-14195 Germany; and || Immunological Medicine Unit, Hammersmith Hospital, London W12 0NN, United Kingdom

Mice rendered deficient for interleukin (IL) 6 by gene targeting were evaluated for their response to T cell–dependent antigens. Antigen-specific immunoglobulin (Ig)M levels were unaffected whereas all IgG isotypes showed varying degrees of alteration. Germinal center reactions occurred but remained physically smaller in comparison to those in the wild-type mice. This concurred with the observations that molecules involved in initial signaling events leading to germinal center formation were not altered (e.g., B7.2, CD40 and tumor necrosis factor R1). T cell priming was not impaired nor was a gross imbalance of T helper cell (Th) 1 versus Th2 cytokines observed. However, B7.1 molecules, absent from wild-type counterparts, were detected on germinal center B cells isolated from the deficient mice suggesting a modification of costimulatory signaling. A second alteration involved impaired de novo synthesis of C3 both in serum and germinal center cells from IL-6–deficient mice. Indeed, C3 provided an essential stimulatory signal for wild-type germinal center cells as both monoclonal antibodies that interrupted C3-CD21 interactions and sheep anti–mouse C3 antibodies caused a significant decrease in antigen-specific antibody production. In addition, germinal center cells isolated from C3–deficient mice produced a similar defect in isotype production. Low density cells with dendritic morphology were the local source of IL-6 and not the germinal center lymphocytes. Adding IL-6 in vitro to IL-6–deficient germinal center cells stimulated cell cycle progression and increased levels of antibody production. These findings reveal that the germinal center produces and uses molecules of the innate immune system, evolutionarily pirating them in order to optimally generate high affinity antibody responses.

Key Words: germinal center • interleukin 6 • complement • antibody • follicular dendritic cells

M.B. Pepys is supported by Programme Grant G97900510. The Basel Institute for Immunology was founded and is supported by F. Hoffmann-La Roche, Basel, Switzerland.

Address all correspondence to M.H. Kosco-Vilbois at her present address: Serono Pharmaceutical Research Institute, 14, chemin des Aulx, CH-1228 Geneva, Switzerland. Phone: 41-22-706-9708. Fax: 41-22-794-6965. E-mail: marie.kosco-vilbois{at}serono.com

S. Herren's present address is Serono Pharmaceutical Research Institute, CH-1228 Geneva, Switzerland.

Abbreviations used: BCR, B cell antigen receptor; FDC, follicular dendritic cell; HA, hemagglutinin; HPRT, hypoxanthine phosphoribosyltransferase; PNA, peanut agglutinin; RT, reverse transcription.


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