G_αq-deficient chimeras develop B cell–dependent systemic autoimmunity. (A and B) Arterial blood from WT and Gnaq^−/− BM chimeras (8 mo after reconstitution) was isolated and complete blood cell counts were performed. Mean red blood cell counts (A) and hemoglobin concentration (B) are reported. Data shown are the mean ± SD of four mice/group and are representative of two independent experiments. P-values were determined using an unpaired Student’s t test. (C) The diameters of ankle and wrist joints were measured in WT and Gnaq^−/− chimeras at 5 mo after reconstitution. Data are represented as the mean ± SD of 8–10 mice/group. Similar results were seen in three experiments. P-values were determined using an unpaired Student’s t test. (D–K) Histological analysis (hematoxylin and eosin [H&E]) of knee and ankle joints from WT and Gnaq^−/− chimeras was performed at 5 mo after reconstitution. (D) Normal knee joint from a WT chimera showing femur (F) and Tibia (T). (E) Knee joint from a Gnaq^−/− chimera with focal soft tissue inflammation (arrow) adjacent to a joint space (S) where the synovial lining is disrupted. A higher power view (F) demonstrates a focus of mixed inflammatory cells (arrow) and necrosis of the overlying synovium. (G) The articular surface of the distal femur of a Gnaq^−/− chimera is irregular, thinned, and covered by fibrous pannus (arrows). (H) Normal ankle joint from a WT chimera. (I) Ankle from a Gnaq^−/− chimera with marked inflammation of soft tissues accompanied by exostotic bone (arrows) and accumulation of fibrin within the joint space (S). (J) Bone from the foot of a Gnaq^−/− chimera with proliferative periostitis overlying an area of bone lysis represented as scalloping of the bone surface (arrows). (K) Higher power of bone from the foot shows multinucleated osteoclasts within resorptive foci (arrows). Images are from one representative animal out of 5–10 mice/group. Bars: (D–J) 100 µm; (K) 20 µm. Two independent experiments were performed. (L) Survival of Gnaq^−/− and WT chimeras was tracked for 6 mo after BM reconstitution. Data are shown as the percentage of survival of each group (n = 10 mice/group). P-values were determined using the Wilcoxon test. Data are representative of three independent experiments. (M) G_αq-deficient and WT chimeras were treated with anti-CD20 (clone 18B12) or control Ab at 2 mo after reconstitution and survival was tracked over the next 11 mo. The experiment was performed once with 10 mice/group. P-values were determined using a Log-rank test.