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. 2022 Mar 24;24(4):565–578. doi: 10.1038/s41556-022-00866-3

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© The Author(s) 2022

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.

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Fig. 6 — a, Enhanced interactions across FL NHC subclusters and malignant B cells (B_malignant). Circle size indicates the negative log₁₀ of adjusted P values (Methods). Circles are coloured when a stroma-derived factor is upregulated in relevant FL subclusters. b, IF staining for MECA-79 (cyan), DCN (red) and CD70 (green) in MFLN and FL samples. Scale bars, 200 μm. Representative images from one of three independent experiments are shown. c, Proportions of CD70⁺ area in medullary and adventitia regions of MFLN (n = 3) and FL (n = 3) samples. Circles represent biologically independent samples. Bars indicate the median. **P = 0.0095 (two-sided unpaired t-test). d, Binding of FL CD19⁺CD10⁺ cells to CD70-Fc protein with an anti-CD27 blocking antibody or isotype human IgG. The histograms represent three independent experiments (FL 13) with the count in arbitrary units. e, Blocking of FL CD19⁺CD10⁺ cell binding to CD70-Fc protein after treating cells with an anti-CD27 blocking antibody (n = 3) or isotype mouse IgG1 (n = 3) in CD27⁺ FL samples (FL 11–FL 14). Proportions of cells bound to CD70-Fc protein were adjusted by subtracting nonspecific binding observed with human IgG. CD70-Fc protein binding to cells treated with isotype mouse IgG1 was set to 100% in each experiment. Circles represent independent experiments. Bars indicate the median. **P = 0.0022, ***P = 7.3 × 10⁻⁴ (FL 11), ***P = 2.2 × 10⁻⁴ (FL 12), ***P = 7.6 × 10⁻⁴ (FL 13) (two-sided paired t-test). f, Representative malignant B-enriched cell (FL 14) adhesion to medullary regions of FL in the presence of an isotype mouse IgG1 or anti-CD27 antibody. Orange dots indicate adherent cells. Yellow dashed lines indicate medullary regions. Scale bars, 200 μm. g, Blocking of malignant B-enriched cell (FL 11, FL 13 and FL 14) adhesion to FL medullary regions (per mm²) after treating cells with an anti-CD27 blocking antibody (n = 3) or isotype mouse IgG1 (n = 3). Adhesion of cells treated with isotype mouse IgG1 was set to 100% in each experiment. Circles represent independent experiments. Bars indicate the median. *P = 0.041 (FL 11), *P = 0.027 (FL 14), **P = 0.0050 (two-sided paired t-test). Statistical source data are provided.

Source data