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ICOS is critical for CD40-mediated antibody class switching.

A J McAdam1, R J Greenwald, M A Levin

  • 1Departments of Pathology, Brigham and Women's Hospital and Harvard Medical School, 221 Longwood Avenue, Boston, Massachusetts 02115, USA.

Nature
|May 9, 2001
PubMed
Summary

Inducible co-stimulatory molecule (ICOS) is crucial for T-cell activation and B-cell collaboration. ICOS-deficient mice show impaired immunoglobulin class switching, highlighting ICOS's role in immune responses.

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Area of Science:

  • Immunology
  • Molecular Biology

Background:

  • Co-stimulatory signals are essential for optimal T-cell activation.
  • The inducible co-stimulatory molecule (ICOS) is a CD28 homologue involved in T-cell differentiation.
  • Existing co-stimulatory pathways like B7-CD28 do not fully explain T-cell activation.

Purpose of the Study:

  • To investigate the essential functions of ICOS in immune responses.
  • To determine the role of ICOS in T-cell and B-cell interactions.

Main Methods:

  • Generation of ICOS-deficient (ICOS-/-) mice.
  • Analysis of immunoglobulin isotype class switching and germinal center formation in ICOS-/- mice.
  • Assessment of class switching restoration upon CD40 stimulation.

Main Results:

  • ICOS-/- mice exhibited significant deficits in immunoglobulin isotype class switching.
  • Germinal center formation was impaired in ICOS-/- mice.
  • CD40 stimulation restored class switching in ICOS-/- mice, indicating ICOS's role in T-cell/B-cell collaboration.

Conclusions:

  • ICOS plays a critical role in immunoglobulin class switching and germinal center formation.
  • ICOS facilitates T-cell/B-cell collaboration, likely through the CD40/CD40L pathway.
  • Understanding ICOS function may lead to new therapies for immune-mediated diseases.