Cd79b p.Y195H augments BCR signaling. (A) Lymphoma cells of MBC and 79-MBC lymphomas were analyzed for levels of phosphorylated PLCg2 and SYK by flow cytometry. Representative cases are visualized as histograms, the geometric mean fluorescence intensity (MFI) is quantified for all analyzed cases (MBC, n = 10; and 79-MBC, n = 7). (B) The levels of phosphorylated PLCg2 and SYK in PPMBC and 79-PPMBC lymphoma cells were determined by flow cytometry. Visualized are representative cases; the MFIs of 12 PPMBC and 18 79-PPMBC lymphoma samples were quantified. (C) PLAs to detect the proximity of MYD88 and CD79B were performed on FFPE samples of PPMBC and 79-PPMBC lymphomas. Before sample collection, the animals were either left untreated or treated acutely with ibrutinib (30mg/kg orally, daily for 3 days). PLA foci are visualized in yellow, and B220 staining (violet) was used to determine cell numbers. The PLA count per cell was quantified for a minimum of 5 independent lymphomas per condition. PLAs were performed in a similar manner to detect the proximity of MYD88 with MALT1 (D) and BTK (E). ∗P ≤ .05, ∗∗P ≤ .01, ∗∗∗P ≤ .001, ∗∗∗∗P ≤ .0001. Welch's 2-tailed t test, Benjamini-Hochberg-correction for multihypothesis testing. APC, allophycocyanin; FFPE, formalin-fixed, paraffin-embedded.