Disrupted B‐lymphocyte development and survival in interleukin‐2‐deficient mice

Summary Interleukin‐2‐deficient (IL‐2−/−) mice develop a spontaneous, progressive, CD4+ T‐cell‐mediated colitis with an age‐related decrease in the number of B lymphocytes. The aim of this study was to determine the mechanisms of B‐cell loss in IL‐2−/− mice. Serum immunoglobulin G1 (IgG1) levels in 8‐week‐old IL‐2−/− mice were above normal but then decreased dramatically with advancing age. Between 8 and 11 weeks of age, the number of B‐cell progenitors (B220+ IgM−) in the bone marrow of IL‐2−/− mice was less than half of those in IL‐2+/+ littermates. By 22 weeks of age, very few progenitor cells remained in the bone marrow of most mice, and spleens were almost devoid of B cells. Likewise, B1 cells were not present in the peritoneal cavity of aged IL‐2−/− mice. Flow cytometry analysis of B‐cell differentiation in the bone marrow suggested a progressive loss of B cells from the most mature to the least mature stages, which was not dependent on IL‐2 receptor‐α (IL‐2Rα) expression. B cells transferred from normal animals had similar survival rates in IL‐2−/− and wild‐type mice. We conclude that conventional B cells in older IL‐2−/− mice are lost by attrition owing to a derangement in B‐cell development. Because B1 cells are less dependent on the bone marrow, a separate mechanism for their loss is suggested.