NR AGOJ
AU Klein,M.A.; Frigg,R.; Flechsig,E.; Raeber,A.J.; Kalinke,U.; Bluethmann,H.; Bootz,F.; Suter,M.; Zinkernagel,R.M.; Aguzzi,A.
TI A crucial role for B cells in neuroinvasive scrapie
QU Nature 1997 Dec 18-25; 390(6661): 687-90
KI Nature. 1997 Dec 18-25;390(6661):662-3. PMID: 9414158
PT journal article
AB Although prion proteins are most efficiently propagated through intracerebral inoculation, peripheral administration has caused the diseases kuru, iatrogenic Creutzfeldt-Jakob disease (CJD), bovine spongiform encephalopathy (BSE) and new-variant CJD. The development of neurological disease after peripheral inoculation depends on prion expansion within cells of the lymphoreticular system. Here we investigate the identity of these cells by using a panel of immune-deficient mice inoculated with prions intraperitoneally: we found that defects affecting only T lymphocytes had no apparent effect, but that all mutations that disrupted the differentiation and response of B lymphocytes prevented the development of clinical scrapie. As an absence of B cells and of antibodies correlates with severe defects in follicular dendritic cells, a lack of any of these three components may prevent the development of clinical scrapie. However, we found that scrapie developed after peripheral inoculation in mice expressing immunoglobulins that were exclusively of the M subclass and without detectable specificity for the normal form of the prion PrPc, and in mice which had differentiated B cells but no functional follicular dendritic cells. We conclude that differentiated B cells are crucial for neuroinvasion by scrapie, regardless of the specificity of their receptors.
ZR 29 Zitate
IN Periphere Scrapie-Infektionen werden nicht behindert, wenn Mäusen lediglich die T-Lymphozyten fehlen. Die Reifung von B-Lymphozyten betreffende Mutationen verhindern hingegen periphere Scrapie-Infektionen. Da die Abwesenheit von B-Lymphozyten oder Antikörpern zu defekten follikulären dendritischen Zellen führen, könnten auch diese für die Weiterleitung peripherer Scrapie-Infektionen erforderlich sein. Die Autoren fanden aber, dass auch Mäuse peripher infiziert werden konnten, die lediglich Antikörper der M-Klasse produzierten oder deren follikuläre dendritische Zellen defekt waren. Demnach scheinen nur reife B-Lymphozyten, nicht jedoch deren follikuläre dendritische Zellen für die Weiterleitung peripherer Scrapie-Infektionen erforderlich zu sein.
MH Animal; B-Lymphocytes/*immunology; Blotting, Western; Brain/pathology; Mice; Mice, Inbred C57BL; Mice, SCID; Prions/immunology; Scrapie/*immunology/pathology/physiopathology; Support, Non-U.S. Gov't
AD Institute of Neuropathology, University of Zürich, Switzerland.
SP englisch
PO England