The Journal of Experimental Medicine
MBL International Tel: 800.200.5459 CLICK HERE
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online August 20, 2007
doi:10.1084/jem.20070264
The Journal of Experimental Medicine, Vol. 204, No. 9, 2047-2051
The Rockefeller University Press, 0022-1007 $30.00
© 2007 Ferrari et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1316K)
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 CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Ferrari, S.
Right arrow Articles by Plebani, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Ferrari, S.
Right arrow Articles by Plebani, A.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?

BRIEF DEFINITIVE REPORT

 Mutations of the Igß gene cause agammaglobulinemia in man

Simona Ferrari1, Vassilios Lougaris2,3, Stefano Caraffi1, Roberta Zuntini1, Jianying Yang4,5, Annarosa Soresina2,3, Antonella Meini2,3, Giantonio Cazzola6,7, Cesare Rossi1, Michael Reth4,5, and Alessandro Plebani2,3

1 Medical Genetics Unit, S. Orsola-Malpighi University Hospital, 40138 Bologna, Italy
2 Department of Pediatrics and 3 Institute of Molecular Medicine A. Nocivelli, University of Brescia, 25123, Brescia, Italy
4 Department of Molecular Immunology, Faculty of Biology, and 5 Max-Planck-Institute for Immunobiology, Albert-Ludwigs-University Freiburg, 79108 Freiburg, Germany
6 Pediatric Pneumology and 7 Cystic Fibrosis Center, Ospedale Civile Maggiore, 37126 Verona, Italy

CORRESPONDENCE Simona Ferrari:simona.ferrari{at}med.unibo.it;OR Alessandro Plebani:plebani{at}med.unibs.it

Agammaglobulinemia is a rare primary immunodeficiency characterized by an early block of B cell development in the bone marrow, resulting in the absence of peripheral B cells and low/absent immunoglobulin serum levels. So far, mutations in Btk, µ heavy chain, surrogate light chain, Ig{alpha}, and B cell linker have been found in 85–90% of patients with agammaglobulinemia. We report on the first patient with agammaglobulinemia caused by a homozygous nonsense mutation in Igß, which is a transmembrane protein that associates with Ig{alpha} as part of the preBCR complex. Transfection experiments using Drosophila melanogaster S2 Schneider cells showed that the mutant Igß is no longer able to associate with Ig{alpha}, and that assembly of the BCR complex on the cell surface is abrogated. The essential role of Igß for human B cell development was further demonstrated by immunofluorescence analysis of the patient's bone marrow, which showed a complete block of B cell development at the pro-B to preB transition. These results indicate that mutations in Igß can cause agammaglobulinemia in man.

Abbreviations used: BCR, B cell receptor; BLNK, B cell linker; EGFP, enhanced GFP; LC, light chain; µHC, µ heavy chain; PE, phycoerythrin; SLC, surrogate LC.

S. Ferrari and V. Lougaris contributed equally to this paper.


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 Reddit Reddit   Add to Technorati Technorati    What's this?




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