Tolerance without clonal expansion: self-antigen-expressing B cells program self-reactive T cells for future deletion

J Immunol. 2008 Oct 15;181(8):5748-59. doi: 10.4049/jimmunol.181.8.5748.

Abstract

B cells have been shown in various animal models to induce immunological tolerance leading to reduced immune responses and protection from autoimmunity. We show that interaction of B cells with naive T cells results in T cell triggering accompanied by the expression of negative costimulatory molecules such as PD-1, CTLA-4, B and T lymphocyte attenuator, and CD5. Following interaction with B cells, T cells were not induced to proliferate, in a process that was dependent on their expression of PD-1 and CTLA-4, but not CD5. In contrast, the T cells became sensitive to Ag-induced cell death. Our results demonstrate that B cells participate in the homeostasis of the immune system by ablation of conventional self-reactive T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, CD / biosynthesis
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, Differentiation / biosynthesis
  • Antigens, Differentiation / genetics
  • Antigens, Differentiation / immunology
  • Autoantigens / biosynthesis
  • Autoantigens / immunology*
  • Autoimmunity / physiology*
  • B-Lymphocytes / immunology*
  • B-Lymphocytes / metabolism
  • CD5 Antigens / biosynthesis
  • CD5 Antigens / genetics
  • CD5 Antigens / immunology
  • CTLA-4 Antigen
  • Cell Proliferation
  • Clonal Deletion / physiology*
  • Gene Expression Regulation / immunology*
  • Homeostasis / immunology
  • Mice
  • Mice, Transgenic
  • Programmed Cell Death 1 Receptor
  • T-Lymphocytes / immunology*
  • T-Lymphocytes / metabolism

Substances

  • Antigens, CD
  • Antigens, Differentiation
  • Autoantigens
  • CD5 Antigens
  • CTLA-4 Antigen
  • Cd5 protein, mouse
  • Ctla4 protein, mouse
  • Pdcd1 protein, mouse
  • Programmed Cell Death 1 Receptor