ICOS is critical for CD40-mediated antibody class switching

Nature. 2001 Jan 4;409(6816):102-5. doi: 10.1038/35051107.


The inducible co-stimulatory molecule (ICOS) is a CD28 homologue implicated in regulating T-cell differentiation. Because co-stimulatory signals are critical for regulating T-cell activation, an understanding of co-stimulatory signals may enable the design of rational therapies for immune-mediated diseases. According to the two-signal model for T-cell activation, T cells require an antigen-specific signal and a second, co-stimulatory, signal for optimal T-cell activation. The co-stimulatory signal promotes T-cell proliferation, lymphokine secretion and effector function. The B7-CD28 pathway provides essential signals for T-cell activation, but does not account for all co-stimulation. We have generated mice lacking ICOS (ICOS-/- ) to determine the essential functions of ICOS. Here we report that ICOS-/- mice exhibit profound deficits in immunoglobulin isotype class switching, accompanied by impaired germinal centre formation. Class switching was restored in ICOS-/- mice by CD40 stimulation, showing that ICOS promotes T-cell/B-cell collaboration through the CD40/CD40L pathway.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antibody Formation
  • Antigens, Differentiation, T-Lymphocyte / genetics
  • Antigens, Differentiation, T-Lymphocyte / physiology*
  • B-Lymphocytes / immunology
  • CD4-Positive T-Lymphocytes / immunology
  • CD40 Antigens / physiology*
  • CD40 Ligand / physiology
  • Gene Targeting
  • Germinal Center / physiology
  • Haptens
  • Hemocyanins / immunology
  • Immunoglobulin Class Switching*
  • Immunoglobulin Isotypes
  • Inducible T-Cell Co-Stimulator Protein
  • Mice
  • T-Lymphocytes / immunology


  • Antigens, Differentiation, T-Lymphocyte
  • CD40 Antigens
  • Haptens
  • Icos protein, mouse
  • Immunoglobulin Isotypes
  • Inducible T-Cell Co-Stimulator Protein
  • trinitrophenyl keyhole limpet hemocyanin
  • CD40 Ligand
  • Hemocyanins