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Disrupted B‐lymphocyte development and survival in interleukin‐2‐deficient mice
Author(s) -
Schultz Michael,
Clarke Stephen H.,
Arnold Larry W.,
Sartor R. Balfour,
Tonkonogy Susan L.
Publication year - 2001
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.2001.01308.x
Subject(s) - bone marrow , progenitor cell , biology , immunology , b cell , peritoneal cavity , lymphocyte , endocrinology , medicine , stem cell , antibody , microbiology and biotechnology , anatomy
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.