Role of Follicular Dendritic Cells in the Regulation of B Cell Proliferation

Freedman, Arnold S.; D, Wang; Phifer, J S; Manié, Serge N.

doi:10.1007/978-3-642-79603-6_5

Cited by 1 publication

(1 citation statement)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…FDCs provide important costimulatory factors which prevent B lymphocytes from undergoing apoptosis (18). Therefore, the detection of severe and extensive lymphocyte apoptosis following treatment with huTNFR:Fc suggested that this was most likely due to a loss of mature FDCs.…”

Section: Discussionmentioning

confidence: 99%

Temporary Blockade of the Tumor Necrosis Factor Receptor Signaling Pathway Impedes the Spread of Scrapie to the Brain

Mabbott

McGovern²,

Jeffrey³

et al. 2002

J Virol

View full text Add to dashboard Cite

Although the transmissible spongiform encephalopathies (TSEs) are neurodegenerative diseases, their agents usually replicate and accumulate in lymphoid tissues long before infection spreads to the central nervous system (CNS). Studies of a mouse scrapie model have shown that mature follicular dendritic cells (FDCs), which express the host prion protein (PrP c ), are critical for replication of infection in lymphoid tissues. In the absence of mature FDCs, the spread of infection to the CNS is significantly impaired. Tumor necrosis factor alpha (TNF-␣) secretion by lymphocytes is important for maintaining FDC networks, and signaling is mediated through TNF receptor 1 (TNFR-1) expressed on FDCs and/or their precursors. A treatment that blocks TNFR signaling leads to the temporary dedifferentiation of mature FDCs, raising the hypothesis that a similar treatment would significantly delay the peripheral pathogenesis of scrapie. Here, specific neutralization of the TNFR signaling pathway was achieved through treatment with a fusion protein consisting of two soluble human TNFR (huTNFR) (p80) domains linked to the Fc portion of human immunoglobulin G1 (huTNFR:Fc). A single treatment of mice with huTNFR:Fc before or shortly after intraperitoneal injection with the ME7 scrapie strain significantly delayed the onset of disease in the CNS and reduced the early accumulation of disease-specific PrP in the spleen. These effects coincided with a temporary dedifferentiation of mature FDCs within 5 days of huTNFR:Fc treatment. We conclude that treatments that specifically inhibit the TNFR signaling pathway may present an opportunity for early intervention in peripherally transmitted TSEs.

show abstract

Section: Discussionmentioning

confidence: 99%