Adhesion through the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and the VLA-4 (CD49d)-VCAM-1 (CD106) pathways prevents apoptosis of germinal center B cells

J Immunol. 1994 Apr 15;152(8):3760-7.

Abstract

In the germinal center (GC), B cells are either selected to become memory cells or are eliminated through the process of programmed cell death. FDC which are intimately associated with the GC B cells are thought to be important in this selection process. Previously, we have shown that the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) and VLA-4 (CD49d)-VCAM-1 (CD106) adhesion pathways are involved in FDC-B cell interaction. In the present study, we have explored whether these adhesive interactions contribute to the process of B cell selection by studying the effects on apoptosis of GC B cells. Using FDC and B cells derived from human tonsils, we found that only B cells adherent to FDC remain viable: disruption of FDC-B-cell clusters with mAb against LFA-1 alpha (CD11a), VLA-4 (CD49d), ICAM-1 (CD54), or VCAM-1 (CD106) results in apoptosis of the B cells. Furthermore, we found that GC B cells, upon adhesion to plastic-coated purified ICAM-1 (CD54) or VCAM-1 (CD106), show diminished apoptosis. Importantly, we observed that, at low concentration, ICAM-1 (CD54) and VCAM-1 (CD106) act synergistically with anti-IgM, in inhibiting apoptosis. Together, our data strongly suggest that adhesion of B cells via the LFA-1 (CD11a/CD18)-ICAM-1 (CD54) pathway and VLA-4 (CD49d)-VCAM-1 (CD106) pathway contributes to B cell selection.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis*
  • B-Lymphocytes / cytology*
  • Cell Adhesion
  • Cell Adhesion Molecules / physiology*
  • Child
  • Dendritic Cells / cytology*
  • Humans
  • Intercellular Adhesion Molecule-1
  • Lymphocyte Function-Associated Antigen-1 / physiology*
  • Palatine Tonsil / cytology*
  • Receptors, Very Late Antigen / physiology*
  • Vascular Cell Adhesion Molecule-1

Substances

  • Cell Adhesion Molecules
  • Lymphocyte Function-Associated Antigen-1
  • Receptors, Very Late Antigen
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1