Age-related depression of FDC accessory functions and CD21 ligand-mediated repair of co-stimulation

Aydar, Yüksel; Balogh, Péter; Tew, John G.; Szakal, Andras K.

doi:10.1002/1521-4141(2002010)32:10<2817::aid-immu2817>3.0.co;2-z

Cited by 70 publications

(49 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Based on previous (27) and present observations, we reasoned that if a major problem with old FDCs relates to an inability to express normal levels of Fc␥RII and bind Ig-Fc, then old FDCs should be able to stimulate B cells lacking Fc␥RII quite normally. It is known that FDCs from Fc␥RIIB Ϫ/Ϫ mice fail to stimulate wildtype B cells where co-cross-linking of BCR and Fc␥RII can occur, but that they stimulate B cells in the Fc␥RIIB Ϫ/Ϫ mice normally (13).…”

Section: Old Fdcs and Fc␥riib ϫ/ϫ B Lymphocytesmentioning

confidence: 75%

“…The mAb FDC-M1 was used to monitor FDC presence (the FDC reticulum) and FDC-M2, which reacts with the C4 fragment of complement associated with the FDC-ICs (30), was used to monitor Ag trapping/retention by FDCs in the FDC reticulum. Our goal was to understand why old FDCs trap less IC, exhibit depressed Ag-specific and costimulatory signals, and support only low level Ab production (3,18,20,27). Results revealed that both the average density of FDC-M1 labeling and the area of FDC reticulum labeled with FDC-M1 were similar in young and old mice.…”

Section: Discussionmentioning

confidence: 99%

“…In a recent study, old FDCs functioned as well as young FDCs when the primary B cell signal was delivered by LPS and when FDCs were incubated with ICs and complement to provide old FDCs with adequate CD21L to engage the B cell coreceptor complex (27). However, BCR and Fc␥RII are not coligated and ITIM signaling does not occur when LPS is the primary stimulator, thus a deficit in Fc␥RII on old FDCs would not be a problem.…”

Section: Complement and Ic-mediated Fdc Ag Stimulationmentioning

confidence: 98%

“…The FDCs were prepared and incubated with ICs and complement as described previously by Aydar et al (27). In brief, OVA and affinity-purified anti-OVA were used to make ICs for use in cultures.…”

Section: Ic Preparation and Incubation Of Fdcs With Ic And Complementmentioning

confidence: 99%

“…Cell cultures were set up by adding enriched FDC preparations to B and T memory lymphocytes as described by Aydar et al (27). In brief, FDCs were isolated from lymph nodes (axillary, lateral axillary, inguinal, popliteal, mesenteric, and para-aortic) of normal young adult mice by using a modification of a previously described procedure (26).…”

Section: Cell Cultures and Elisamentioning

confidence: 99%

See 4 more Smart Citations

Altered Regulation of FcγRII on Aged Follicular Dendritic Cells Correlates with Immunoreceptor Tyrosine-Based Inhibition Motif Signaling in B Cells and Reduced Germinal Center Formation

Aydar¹,

Balogh²,

Tew

et al. 2003

The Journal of Immunology

Self Cite

View full text Add to dashboard Cite

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, FcγRII, and FDC-M2 on FDCs was immunohistochemically quantitated in draining lymph nodes of actively immunized mice for 10 days after Ag challenge. Initially, FDC FcγRII levels were similar but by day 3 a drastic reduction in FDC-FcγRII 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 FcγRII, were incapable of preventing immunoreceptor tyrosine-based inhibition motif signaling in wild-type B cells but old FDCs stimulated B cells from FcγRIIB−/− 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.

show abstract

Section: Old Fdcs and Fc␥riib ϫ/ϫ B Lymphocytesmentioning

confidence: 75%

Section: Discussionmentioning

confidence: 99%

Section: Complement and Ic-mediated Fdc Ag Stimulationmentioning

confidence: 98%

Section: Ic Preparation and Incubation Of Fdcs With Ic And Complementmentioning

confidence: 99%

Section: Cell Cultures and Elisamentioning

confidence: 99%

See 3 more Smart Citations