Figure 8. Stroma-derived Dll1 Notch ligands drive B cell transdifferentiation and plasma cell differentiation in lymphopenic recipients.
B6 versus Rag2–/– versus Rag2–/– crossed to Ccl19-Cre Dll1fl/fl hosts were treated with isotype control or anti-Dll1 antibodies at days 0, 3, and 6 after transfer of purified B6-CD45.1 FoB cells. Flow cytometry and immunofluorescence imaging were performed on recipient splenocytes at day 8 after transfer. (A) Representative flow cytometry plots depicting live CD45.1+CD19+CD93– donor-derived mature B cells recovered at day 8 from B6 or indicated Rag2–/– recipients. (B) Percentage and (C) absolute numbers of CD45.1+ MZB cells at day 8 in each recipient group. (D) Histograms depicting cell surface expression of markers and CTV dilution on donor derived CD45.1+ B cells in B6 (black), Rag2–/– (red), or indicated Rag2–/– recipients. (E) Representative flow cytometry plots showing live donor-derived CD138+ plasma cells at day 8 in B6 or indicated Rag2–/– recipients. (F) Percentage and (G) absolute numbers of donor-derived plasma cells at day 8 in each recipient group. (H) Immunofluorescence microscopy of spleen sections of B6, Rag2–/–, and Rag2–/– Ccl19-Cre Dll1fl/fl recipients at day 8 after adoptive transfer, with labeled CD45.1+ cells (green), CTV (blue), CD169 (white), and laminin (red). Dotted regions are magnified in the second row of images. Scale bars: 50 μm. Data are from 2 independent experiments. (B, F, and G) *P < 0.05, **P < 0.01, and ****P < 0.0001, by 1-way ANOVA. Each data point represents an individual mouse.