Global analysis of B cell selection using an immunoglobulin light chain-mediated model of autoreactivity. Academic Article uri icon

Overview

abstract

  • The important subtleties of B cell tolerance are best understood in a diverse immunoglobulin (Ig) repertoire context encoding a full spectrum of autoreactivity. To achieve this, we used mice expressing Igκ transgenes that confer varying degrees of autoreactivity within a diverse heavy chain (HC) repertoire. These transgenes, coupled with a biomarker to identify receptor-edited cells and combined with expression cloning of B cell receptors, allowed us to analyze tolerance throughout B cell development. We found that both the nature of the autoantigen and the Ig HC versus light chain (LC) contribution to autoreactivity dictate the developmental stage and mechanism of tolerance. Furthermore, although selection begins in the bone marrow, over one third of primary tolerance occurs in the periphery at the late transitional developmental stage. Notably, we demonstrate that the LC has profound effects on tolerance and can lead to exacerbated autoantibody production.

publication date

  • December 24, 2012

Research

keywords

  • B-Lymphocytes
  • Immune Tolerance
  • Immunoglobulin Light Chains

Identity

PubMed Central ID

  • PMC3549719

Scopus Document Identifier

  • 84874526021

Digital Object Identifier (DOI)

  • 10.1016/j.molimm.2004.07.049

PubMed ID

  • 23267014

Additional Document Info

volume

  • 210

issue

  • 1