Optimal germinal center responses require a multistage T cell:B cell adhesion process involving integrins, SLAM-associated protein, and CD84

Immunity. 2010 Feb 26;32(2):253-65. doi: 10.1016/j.immuni.2010.01.010. Epub 2010 Feb 11.

Abstract

CD4(+) T cells deficient in signaling lymphocyte activation molecule (SLAM)-associated protein (SAP) exhibit a selective impairment in adhesion to antigen-presenting B cells but not dendritic cells (DCs), resulting in defective germinal center formation. However, the nature of this selective adhesion defect remained unclear. We found that whereas T cell:DC interactions were primarily integrin dependent, T cell:B cell interactions had both an early integrin-dependent phase and a sustained phase that also required SAP. We further found that the SLAM family member CD84 was required for prolonged T cell:B cell contact, optimal T follicular helper function, and germinal center formation in vivo. Moreover, both CD84 and another SLAM member, Ly108, mediated T cell adhesion and participated in stable T cell:B cell interactions in vitro. Our results reveal insight into the dynamic regulation of T cell:B cell interactions and identify SLAM family members as critical components of sustained T cell:B cell adhesion required for productive humoral immunity.

Publication types

  • Research Support, N.I.H., Intramural

MeSH terms

  • Animals
  • Antigens, CD / genetics
  • Antigens, CD / immunology
  • Antigens, CD / metabolism
  • Antigens, Ly / immunology
  • Antigens, Ly / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism*
  • B-Lymphocytes / pathology
  • Cell Adhesion / genetics
  • Cell Adhesion / immunology*
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology
  • Cell Proliferation
  • Cells, Cultured
  • Germinal Center / metabolism*
  • Germinal Center / pathology
  • Interferon-gamma / metabolism
  • Interleukins / metabolism
  • Intracellular Signaling Peptides and Proteins / genetics
  • Intracellular Signaling Peptides and Proteins / immunology
  • Intracellular Signaling Peptides and Proteins / metabolism*
  • Lymphocyte Activation / genetics
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / immunology
  • Receptors, Cell Surface / metabolism
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signaling Lymphocytic Activation Molecule Family
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • T-Lymphocytes / immunology
  • T-Lymphocytes / metabolism*
  • T-Lymphocytes / pathology

Substances

  • Antigens, CD
  • Antigens, Ly
  • Cd84 protein, mouse
  • Interleukins
  • Intracellular Signaling Peptides and Proteins
  • Ly108 protein, mouse
  • Receptors, Cell Surface
  • SLAMF6 protein, human
  • Sh2d1a protein, mouse
  • Signaling Lymphocytic Activation Molecule Associated Protein
  • Signaling Lymphocytic Activation Molecule Family
  • Slamf6 protein, mouse
  • Signaling Lymphocytic Activation Molecule Family Member 1
  • Interferon-gamma
  • interleukin-21