Loss of NIAM promotes reactive lymphoid hyperplasia and B-cell lymphoma in the spleen.

<p><b>A</b>. Weights of spleens from +/+ and +/m mice (CON, n = 15) compared to <i>NIAM^m/m</i> mice (m/m, n = 12). Note: one WT (+/+) mouse with an incidental case of severe chronic pyometra was excluded from the analysis. Statistical significance was shown by a Mann-Whitney test (*, p<0.05) <b>B</b>. The percentage of splenic white pulp per total splenic area was calculated for each genotype. <i>NIAM^m/m</i> mice (n = 8) are statistically different from both wild-type (+/+, n = 5) and heterozygous (+/m, n = 6) mice as calculated by an unpaired two-tailed T-test. (*, p<0.05) Note: one WT (+/+) and one mutant (m/m) mouse were excluded from the analysis because extensive extramedullary hematopoiesis prevented accurate visualization of the white pulp <b>C</b>. Representative images of spleens from control wild-type (+/+) and homozygous m/m mice (H&E, 40x). Splenic white pulp (asterisks) was increased in <i>NIAM^m/m</i> mice. Note: these samples show a range of variation in the extent of red pulp extramedullary hematopoiesis that was seen for both groups. <b>D</b>. Eosinophilic crystalline pneumonia in the lungs of control <i>NIAM^+/m</i> heterozygous and <i>NIAM^m/m</i> mice. Loss of NIAM resulted in more severe disease with extensive pulmonary lymphoid inflammation (arrows) and large extracellular crystals (asterisks) in the affected <i>NIAM^m/m</i> mouse. (H&E, 40× top and 100× bottom panels) <b>E</b>. White pulp from control <i>NIAM^+/m</i> heterozygous and <i>NIAM^m/m</i> homozygous mice (H&E, 600x). A spleen from a heterozygous mouse with chronic ulcerative dermatitis and reactive hyperplasia of white pulp characterized by a germinal center (GC) and tingible body macrophages full of cellular debris (arrows) on a background of small lymphocytes (SL) (left panel). In two homozygous m/m mice, typical white pulp architecture was multifocally depleted and effaced by centroblasts and centrocytes with multiple mitotic figures (inset and arrows) (right panel). Note that <i>NIAM^+/m</i> heterozygous and <i>NIAM^+/+</i> wild-type mice appeared identical in our analyses and were therefore used interchangeably as controls.