The Journal of Experimental Medicine
for flow cytometry > invitrogen
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 144K)
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 Takahashi, Y.
Right arrow Articles by Kelsoe, G.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Takahashi, Y.
Right arrow Articles by Kelsoe, G.
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, 0022-1007/1999/8/399/ $5.00
The Journal of Experimental Medicine, Volume 190, Number 3, August 2, 1999 399-410

Original Article

Relaxed Negative Selection in Germinal Centers and Impaired Affinity Maturation in bcl-xL Transgenic Mice

Yoshimasa Takahashia, Douglas M. Cerasolia, Joseph M. Dal Portoa, Michiko Shimodaa, Robert Freunda, Wei Fangb, David G. Telanderb, Erika-Nell Malveyb, Daniel L. Muellerb, Timothy W. Behrensb, and Garnett Kelsoec

a From the Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, Maryland 21201
b Center for Immunology, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455
c Department of Immunology, Duke University Medical Center, Durham, North Carolina 27710
Department of Immunology, Box 3010, Duke University Medical Center, Durham, NC 27710.919-613-7878919-613-7936

ghkelsoe{at}duke.edu

The role of apoptosis in affinity maturation was investigated by determining the affinity of (4-hydroxy-3-nitrophenyl)acetyl (NP)-specific antibody-forming cells (AFCs) and serum antibody in transgenic mice that overexpress a suppressor of apoptosis, Bcl-xL, in the B cell compartment. Although transgenic animals briefly expressed higher numbers of splenic AFCs after immunization, the bcl-xL transgene did not increase the number or size of germinal centers (GCs), alter the levels of serum antibody, or change the frequency of NP-specific, long-lived AFCs. Nonetheless, the bcl-xL transgene product, in addition to endogenous Bcl-xL, reduced apoptosis in GC B cells and resulted in the expansion of B lymphocytes bearing VDJ rearrangements that are usually rare in primary anti-NP responses. Long-lived AFCs bearing these noncanonical rearrangements were frequent in the bone marrow and secreted immunoglobulin G1 antibodies with low affinity for NP. The abundance of noncanonical cells lowered the average affinity of long-lived AFCs and serum antibody, demonstrating that Bcl-xL and apoptosis influence clonal selection/maintenance for affinity maturation.

Key Words: Bcl-xL • apoptosis • affinity maturation • germinal center • clonal selection

1used in this paper: AFC, antibody-forming cell; BCR, B cell antigen receptor; BM, bone marrow; BrdU, 2-bromodeoxyuridine; CG, chicken {gamma}-globulin; ELISPOT, enzyme-linked immunospot; FDC, follicular dendritic cell; GC, germinal center; HRP, horseradish peroxidase; mIg, membrane Ig; NP, (4-hydroxy-3-nitrophenyl)acetyl; PNA, peanut agglutinin; R/S ratio, ratio of replacement to silent mutations; TUNEL, terminal deoxynucleotidyl transferase–mediated dUTP-biotin nick end labeling

© 1999 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?




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