Development of a non-clonal, low-grade B-cell LPD in MYD88^L265Pmice. (A) Kaplan-Meier plots illustrating event-free survival of aging cohorts of AID^Cre (n = 13), MYD88^WT (n = 12), and MYD88^L265P (n = 28) mice. P value was calculated by using a log-rank test. (B) Spleen weights in aged AID^Cre (n = 5) and MYD88^WT (n = 5) control mice and MYD88^L265P (n = 11) mice with LPD. Graphs depict the mean ± SD. P values were calculated by using Welch’s t test. (C) Gross images of spleens and LNs from representative MYD88^L265P mice with low-grade B-cell LPD. Scale bar, 1 cm. Histologic and IHC stains of indicated markers on serial spleen (D), LN (E), and BM (F) sections from representative, age-matched AID^Cre and MYD88^WT control mice, and 1 MYD88^L265P mouse with LPD. Note expansion of plasmacytoid lymphocytes (white arrowheads) in the MYD88^L265P mice compared with controls; and punctate, cytoplasmic MYD88 staining in the MYD88^L265P LPD cells (black arrowheads). Scale bars: white, 50 µm; black, 500 µm; yellow, 5 µm (see also supplemental Figure 2B). (G) Clonality evaluated by Southern blot analysis of the IgH gene in DNA isolated from LNs of MYD88^L265P (n = 7) mice with LPD. GL, non-rearranged germline band.