A transgenic murine lymphoplasmacytic/WM model points toward a role for Treg in supporting WM biology. (A) Representative flow cytometry analyses showing the percentages of B220⁺CD138⁻ B cells, B220⁺CD138⁺ plasmablasts, and B220⁻CD138⁺ plasma cells in the BM of M88B2m transgenic mice developing lymphoplasmacytic lymphoma/WM in comparison with mb1-cre control mice. (B) Representative serum protein electrophoresis images of M88B2m and control mice. One representative image is shown. Quantification of gamma fractions is represented. (right) Enzyme-linked immunosorbent assay in serum of M88B2m mice compared with control mice (n = 6 per cohort) measuring the levels of secreted IgM.(C) Flow cytometry analyses of CD4⁺ and CD8⁺ T-cell subsets, including CD62L⁺CD44^– naïve subpopulations. Quantification of the percentage of CD4⁺ and CD8⁺ T cells with expression of PD-1 or TIGIT (n = 6-10 mice per cohort) is also shown. (D) Representative flow cytometry analyses measuring the percentage of CD4⁺CD25⁺Foxp3⁺ Tregs in M88B2m mice (n = 10) compared with control mice (n = 6). (E) Ex vivo coculturing assays including Tregs isolated from healthy mice with lymphoma B cells from M88B2m mice or control B lymphocytes. Quantification of Ki67⁺ vs Ki67⁻ Treg numbers are shown for each coculture (n = 2 independent experiments, each in duplicate). ∗P < .05; ∗∗P < .01; and ∗∗∗P < .001.