CD21-deficient mice contained fewer splenic prions than CD35 knockout mice early after infection that contributed to delayed prion neuroinvasion and terminal disease, despite forming follicular networks closer to proximal nerves. However, mice lacking CD21 succumbed to terminal prion disease significantly later than mice lacking CD35 or wild-type and hemizygous mice. Here we show that both isoforms act as high-affinity cell surface prion receptors. In mouse models, genetic depletion of Cr2 causes either a delay or complete prevention of prion disease, but the relative importance of CD35 versus CD21 in promoting prion disease remains unknown. Differential splicing of transcripts from the mouse Cr2 gene generates isoforms with both shared and unique complement binding capacities and cell-type expression. CD21 helps activate B cells as part of the B cell coreceptor with CD19 and CD81. CD35 stimulates phagocytosis on macrophages and antigen presentation on follicular dendritic cells (FDCs). Pixelmator Pro 3.3.Complement receptors 1 and 2 (CR1/2 or CD35/CD21) recognize complement-opsonized antigens to initiate innate and adaptive immunity, respectively.Luminar Neo 1.7.0 (14059) posted on Febru| under Application.Wondershare UniConverter 14.2.11.30 posted on Ma| under Application, Utilities.BetterDisplay Pro 1.4.3 posted on Febru| under Application.MouseBoost PRO 2.6.4 posted on Ma| under Application.Adobe Acrobat DC Pro 2022.001.20112 posted on Ap| under Adobe, Application.Adobe Lightroom Classic v11.5 posted on Aug| under Adobe, Application, Graphics & Design, Photography.Adobe Premiere Pro 2022 v22.6 posted on Aug| under Adobe, Application, Video.Topaz Video AI 3.1.7 posted on Ma| under Application.Adobe Illustrator 2023 27.0 posted on Octo| under Adobe, Application, Graphics & Design.Final Cut Pro 10.6.5 posted on Octo| under Apple, Application, Video.CleanMyMac X 4.10.6 posted on | under Application, Utilities.Parallels Desktop Business Edition 18.1.1 (53328) posted on Janu| under Application, Utilities.
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