A r t i c l e T cells (unpublished data). By 24 wk of age, however, the DKO female mice, but not the DKO male mice, were found to develop splenomegaly and lymphadenopathy (Fig. 1, A and B). None of the WT, Def6tr/tr, or Swap-70/ female or male mice developed similar findings (Fig. 1, A and B). Thus, the concomitant absence of DEF6 and SWAP-70 results in the spontaneous development of a lymphoprolif- erative disorder that selectively affects the female gender. To better characterize the lymphoproliferative disease exhibited by the DKO female mice, a detailed flow cytomet- ric analysis was conducted. Spleens of 24-wk-old DKO female mice demonstrated a significant expansion of effector Figure 1. Spontaneous development of lymphoproliferation in DKO female mice. (A) Representative spleen and lymph nodes from 8- and 24-wk- old C57BL/6 (WT), Swap-70/ (S70/), Def6tr/tr, and Def6tr/trSwap-70/ (DKO) female mice. Data are representative of six independent experiments with one mouse/group. (B) Total number of splenic cells in 24-wk-old female (F) and male (M) mice. For female mice, data represent six independent experi- ments with one mouse/group. For male mice, data represent three independent experiments with one mouse/group. (C–H) Total number of splenic CD4+ T cells (C), CD4+CD62LloCD44hi T cells (D), CD4+ICOS+ T cells (E), B220+ B cells (F), B220+PNA+ B cells (G), and B220loCD138+ B cells (H) in 24-wk-old female mice as assessed by flow cytometry. Each dot represents an individual mouse. Horizontal bars indicate mean for each group. Data are representative of six independent experiments with one mouse/group. (I) Immunofluorescence analysis of GCs and plasma cells in the indicated mice. Spleens were stained for GCs with B220 (red) and PNA (green) in the top panels or for plasma cells with B220 (red) and CD138 (green) in the bottom panels. Magnification is 16×. Bar, 500 µm. Data are representative of three independent experiments with one mouse/group. *, P < 0.05; **, P < 0.01; ***, P < 0.005; ns, not statistically significant. JEM Vol. 209, No. 3 583