Altered regulation of Fc gamma RII on aged follicular dendritic cells correlates with immunoreceptor tyrosine-based inhibition motif signaling in B cells and reduced germinal center formation.
Aging is associated with reduced trapping of Ag in the form of in immune complexes (ICs) by follicular dendritic cells (FDCs). We postulated that this defect was due to altered regulation of IC trapping receptors. The level of FDC-M1, complement receptors 1 and 2, FcgammaRII, and FDC-M2 on FDCs was immunohistochemically quantitated in draining lymph nodes of actively immunized mice for 10 days after Ag challenge. Initially, FDC FcgammaRII levels were similar but by day 3 a drastic reduction in FDC-FcgammaRII expression was apparent in old mice. FDC-M2 labeling, reflecting IC trapping, was also reduced and correlated with a dramatic reduction in germinal center (GC) B cells as indicated by reduced GC size and number. Nevertheless, labeling of FDC reticula with FDC-M1 and anti-complement receptors 1 and 2 was preserved, indicating that FDCs were present. FDCs in active GCs normally express high levels of FcRs that are thought to bind Fc portions of Abs in ICs and minimize their binding to FcRs on B cells. Thus, cross-linking of B cell receptor and FcR via IC is minimized, thereby reducing signaling via the immunoreceptor tyrosine-based inhibition motif. Old FDCs taken at day 3, when they lack FcgammaRII, were incapable of preventing immunoreceptor tyrosine-based inhibition motif signaling in wild-type B cells but old FDCs stimulated B cells from FcgammaRIIB(-/-) mice to produce near normal levels of specific Ab. The present data support the concept that FcR are regulated abnormally on old FDCs. This abnormality correlates with a reduced IC retention and with a reduced capacity of FDCs to present ICs in a way that will activate GC B cells.
Aydar
Yüksel
Y
Department of Anatomy and Neurobiology, The Immunology Group, Virginia Commonwealth University, Medical College of Virginia, Richmond, VA 23298, USA.
Balogh
Péter
P
Tew
John G
JG
Szakal
Andras K
AK
D000375:Aging / Q000276:immunology*; D020816:Amino Acid Motifs / Q000276:immunology; D000818:Animals; D000911:Antibodies, Monoclonal / Q000032:analysis; D000936:Antigen-Antibody Complex / Q000502:physiology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D016922:Cellular Senescence / Q000276:immunology; D020566:Dendritic Cells, Follicular / Q000276:immunology* / Q000378:metabolism*; D015536:Down-Regulation / Q000276:immunology*; D018858:Germinal Center / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008213:Lymphocyte Activation / Q000235:genetics; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D018345:Mice, Knockout; D019887:Peanut Agglutinin / Q000032:analysis; D010567:Pertussis Vaccine / Q000008:administration & dosage / Q000276:immunology; D017463:Receptors, Complement 3b / Q000032:analysis; D017464:Receptors, Complement 3d / Q000032:analysis; D017452:Receptors, IgG / Q000096:biosynthesis*; D015398:Signal Transduction / Q000276:immunology; D014443:Tyrosine / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D000936:Antigen-Antibody Complex; D019887:Peanut Agglutinin; D010567:Pertussis Vaccine; D017463:Receptors, Complement 3b; D017464:Receptors, Complement 3d; D017452:Receptors, IgG; D014443:Tyrosine