Follicular dendritic cell (FDC)-FcgammaRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development

Eur J Immunol. 2006 Oct;36(10):2715-24. doi: 10.1002/eji.200636122.

Abstract

Follicular dendritic cell (FDC)-FcgammaRIIB levels are up-regulated 1-3 days after challenge of actively immunized mice with Ag. This kinetics suggested that memory cells are not driving this response, prompting the hypothesis that immune complex (IC)-FDC interactions lead to FDC activation. To test this, mice passively immunized with anti-OVA Ab were OVA challenged to produce IC. After 3 days, levels of IC, FcgammaRIIB, ICAM-1, and VCAM-1 on FDC were analyzed. FDC were also stimulated with IC in vitro, and mRNA for FcgammaRIIB, ICAM-1, and VCAM-1 was quantified by quantitative RT-PCR. IC labeling in passively immunized WT and FcgammaRIIB-/- mice revealed five to six FDC-reticula per LN midsagittal section. In WT mice, these IC-bearing FDC-reticula corresponded with FDC-reticula labeling for FcgammaRIIB, ICAM-1, and VCAM-1. Increases in these molecules on IC-stimulated FDC were confirmed by flow cytometry. In marked contrast, in FcgammaRIIB-/- mice, no increased VCAM-1 or ICAM-1 was seen on IC-bearing FDC-reticula or on purified FDC. Addition of IC in vitro resulted in dramatic increases in mRNA for FcgammaRIIB, ICAM-1 and VCAM-1 in WT FDC, but not in FDC from FcgammaRIIB-/- mice, 2.4G2-pretreated WT FDC, B cells, or macrophages. Thus, although FDC-FcgammaRIIB was not essential for IC trapping, engagement of FDC-FcgammaRIIB with IC initiated an FDC activation pathway.

Publication types

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

MeSH terms

  • Animals
  • Antigen-Antibody Complex / immunology*
  • Antigen-Antibody Complex / metabolism
  • B-Lymphocytes / immunology
  • B-Lymphocytes / metabolism
  • Dendritic Cells, Follicular / immunology*
  • Dendritic Cells, Follicular / metabolism
  • Flow Cytometry
  • Immunohistochemistry
  • Intercellular Adhesion Molecule-1 / metabolism
  • Lymph Nodes / cytology
  • Lymph Nodes / immunology
  • Macrophages / immunology
  • Macrophages / metabolism
  • Mice
  • Mice, Mutant Strains
  • Phenotype
  • RNA, Messenger / analysis
  • Receptors, IgG / immunology*
  • Receptors, IgG / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Vascular Cell Adhesion Molecule-1 / metabolism

Substances

  • Antigen-Antibody Complex
  • Fcgr2b protein, mouse
  • RNA, Messenger
  • Receptors, IgG
  • Vascular Cell Adhesion Molecule-1
  • Intercellular Adhesion Molecule-1