The Journal of Experimental Medicine
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text (PDF, 1317K)
Right arrow Alert me when this article is cited
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 Rudich, S. M.
Right arrow Articles by Mongini, P. K.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Rudich, S. M.
Right arrow Articles by Mongini, P. K.
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?

Journal of Experimental Medicine, Vol 168, 247-266, Copyright © 1988 by Rockefeller University Press

ARTICLES

Anti-IgM-mediated B cell signaling. Molecular analysis of ligand binding requisites for human B cell clonal expansion and tolerance

SM Rudich, KH Roux, RJ Winchester and PK Mongini
Department of Rheumatic Diseases, Hospital for Joint Diseases, New York University Medical School, New York 10003.

The ligand binding requisites for membrane IgM-mediated signaling of human B lymphocyte clonal expansion and B cell tolerance were investigated with a well-characterized set of soluble murine anti-human IgM mAbs. Evaluation of the impact of mu chain domain specificity, affinity, and binding stoichiometry for membrane IgM on antibody- induced regulation of normal and leukemic B cell DNA synthesis revealed that the ligand binding requisites for inducing or, alternatively, suppressing B cell DNA synthesis are significantly different. First, while the induction of S phase entry required micrograms/ml concentrations of ligand, orders of magnitude lower concentrations of ligand sufficed for inhibitory signaling. Second, while an upper affinity threshold for achieving maximal stimulation of B cell DNA synthesis was never detected, inhibitory signaling by bivalent ligands appeared to become relatively affinity independent at Fab binding affinities greater than 7.0 x 10(6) M-1. Third, while a C mu 1-specific mAb with an enhanced incidence of monogamous binding to mIgM was ineffective at inducing B cell DNA synthesis, the antibody was not significantly compromised in ability to initiate inhibitory signals. These differences could be observed in a clonal B cell population which positively or negatively responded to mIgM ligation depending upon its state of activation. The accumulated observations indicate that the ligand binding requisites for inhibitory signal transduction in human B lymphocytes are much less rigorous than those for stimulatory signal transduction and suggest that many physiologically relevant anti-Ig antibodies are more likely to function in the negative feedback regulation of B cell responses than in the direct triggering of human B cell clonal expansion.
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