Follicular dendritic cell (FDC)-FcgammaRIIB engagement via immune complexes induces the activated FDC phenotype associated with secondary follicle development.
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.
El Shikh
Mohey Eldin
ME
Department of Microbiology and Immunology, Virginia Commonwealth University, Richmond, VA 23298-0678, USA.
El Sayed
Rania
R
Szakal
Andras K
AK
Tew
John G
JG
D000818:Animals; D000936:Antigen-Antibody Complex / Q000276:immunology* / Q000378:metabolism; D001402:B-Lymphocytes / Q000276:immunology / Q000378:metabolism; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism; D005434:Flow Cytometry; D007150:Immunohistochemistry; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008817:Mice, Mutant Strains; D010641:Phenotype; D012333:RNA, Messenger / Q000032:analysis; D017452:Receptors, IgG / Q000276:immunology* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D019010:Vascular Cell Adhesion Molecule-1 / Q000378:metabolism
D000936:Antigen-Antibody Complex; C499172:Fcgr2b protein, mouse; D012333:RNA, Messenger; D017452:Receptors, IgG; D019010:Vascular Cell Adhesion Molecule-1; D018799:Intercellular Adhesion Molecule-1