The Journal of Experimental Medicine
IN Cell Analyzer 2000
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online
doi:10.1084/jem.20060964
The Journal of Experimental Medicine, Vol. 204, No. 3, 645-655
The Rockefeller University Press, 0022-1007 $30.00
© van Zelm et al.
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 3168K)
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 van Zelm, M. C.
Right arrow Articles by van Dongen, J. J.M.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by van Zelm, M. C.
Right arrow Articles by van Dongen, J. J.M.
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?

ARTICLE

 Replication history of B lymphocytes reveals homeostatic proliferation and extensive antigen-induced B cell expansion

Menno C. van Zelm1,2, Tomasz Szczepanski1,3, Mirjam van der Burg1, and Jacques J.M. van Dongen1

1 Erasmus MC, Department of Immunology and 2 Department of Pediatrics, 3015 GE Rotterdam, Netherlands
3 Department of Pediatric Hematology and Oncology, Silesian Medical Academy, 41-800 Zabrze, Poland

CORRESPONDENCE J.J.M. van Dongen: j.j.m.vandongen{at}erasmusmc.nl

The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro proliferation studies. We demonstrate that naive mature B lymphocytes, but not transitional B lymphocytes, undergo in vivo homeostatic proliferation in the absence of somatic mutations in the periphery. T cell–dependent B cell proliferation was substantially higher and showed higher frequencies of somatic hypermutation than T cell–independent responses, fitting with the robustness and high affinity of T cell–dependent antibody responses. More extensive proliferation and somatic hypermutation in antigen-experienced B lymphocytes from human adults compared to children indicated consecutive responses upon additional antigen exposures. Our combined observations unravel the contribution of proliferation to both B lymphocyte homeostasis and antigen-induced B cell expansion. We propose an important role for both processes in humoral immunity. These new insights will support the understanding of peripheral B cell regeneration after hematopoietic stem cell transplantation or B cell–directed antibody therapy, and the identification of defects in homeostatic or antigen-induced B cell proliferation in patients with common variable immunodeficiency or another antibody deficiency.

Abbreviations used: CSR, class switch recombination; Ig{kappa}REHMA, Ig{kappa} restriction enzyme hot-spot mutation assay; KREC, kappa-deleting recombination excision circle; MZ, marginal zone; RQ-PCR real-time quantitative PCR; SHM, somatic hypermutation; TREC, T cell receptor excision circle.


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