Fig. 1: Active RANK and TCL1 signaling in B-cells causes a plasma cell disorder.

a Breeding scheme to generate TC-RK mice. Scheme was generated with BioRender.com. b Percentage of CD19⁺CD5⁺ of total viable lymphocytes in the peripheral blood of 12- and 24- week-old animals (n = 3–17 per genotype) determined by flow cytometry. Wildtype and CD19^Cre animals are pooled as wt. Data was pooled from more than three experiments. c Kaplan-Meier overall survival analysis of TC-RK (n = 14), TC (n = 13), RK (n = 16) and wt (n = 17) control mice. For statistical analysis, p value of the log-rank test is shown. d Macroscopic appearance of representative spleens and lymph nodes (left) and dot plot graph (right) depicts spleen (SP) weight in gram (g) of diseased or aged mice with indicated genotypes (n = 4–11 per genotype). e Percentage of CD19⁺CD5⁺ of viable cells in the peripheral blood (PB, left, n = 5–11 per genotype) and SP (right, n = 5–13 per genotype) from animals with indicated genotypes upon signs of disease or aged mice. f Representative flow cytometric analysis of GFP and CD19 expression on viable splenocytes from a diseased TC-RK mouse. g Percentages of GFP^hiCD19^neg cells of viable cells from BM, SP, PB and LI isolated from diseased TC-RK mice (n = 6–13 per organ) compared to aged RK mice (n = 5–6 per organ). h Percentages of CD138⁺B220^low cells of viable cells from bone marrow (BM) from diseased TC-RK mice and diseased or aged control mice (n = 3–10 per genotype). i Percentages of CD138⁺B220^low cells of viable splenocytes cells from diseased TC-RK mice and diseased or aged control mice (n = 3–9 per genotype). j Percentages of CD138⁺B220^low cells of viable cells from liver (LI) of diseased TC-RK mice and diseased or aged control mice (n = 3–6 genotype). k Representative histograms of forward scatter area (FSC-A), surface RANK, CD138, B220, IgM and IgD, as well as intracellular IRF4 and BLIMP1 from GFP^hiCD19^neg cells (green) compared to GFP⁺CD19⁺ cells (black) from TC-RK mice. l Representative images of CD138 immunohistochemistry from bone of a diseased TC-RK mouse (scale bars: overview = 2 mm, detailed image with 20x magnification = 200 μm). Statistical analysis was performed using Student’s t-test and the one-way ANOVA with Tukey correction for multiple comparison. The p values are indicated in respective graphs. All data are presented as mean ± standard deviation.