Censoring of self-reactive B cells by follicular dendritic cell-displayed self-antigen

J Immunol. 2013 Aug 1;191(3):1082-90. doi: 10.4049/jimmunol.1201569. Epub 2013 Jul 1.

Abstract

In the secondary lymphoid organs, intimate contact with follicular dendritic cells (FDCs) is required for B cell retention and Ag-driven selection during the germinal center response. However, selection of self-reactive B cells by Ag on FDCs has not been addressed. To this end, we generated a mouse model to conditionally express a membrane-bound self-antigen on FDCs and to monitor the fate of developing self-reactive B cells. In this article, we show that self-antigen displayed on FDCs mediates effective elimination of self-reactive B cells at the transitional stage. Notwithstanding, some self-reactive B cells persist beyond this checkpoint, showing evidence of Ag experience and intact proximal BCR signaling, but they are short-lived and unable to elicit T cell help. These results implicate FDCs as an important component of peripheral B cell tolerance that prevents the emergence of naive B cells capable of responding to sequestered self-antigens.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adoptive Transfer
  • Animals
  • Antigen-Antibody Complex / immunology
  • Apoptosis / immunology
  • Autoantigens / immunology*
  • Autoimmunity*
  • B-Lymphocytes / immunology*
  • Cell Proliferation
  • Cells, Cultured
  • Dendritic Cells, Follicular / immunology*
  • Lymphocyte Activation
  • Mice
  • Mice, Transgenic
  • Receptors, Antigen, B-Cell / metabolism
  • Signal Transduction / immunology

Substances

  • Antigen-Antibody Complex
  • Autoantigens
  • Receptors, Antigen, B-Cell