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 w
ith advancing age. Between 8 and 11 weeks of age, the number of B-cell prog
enitors (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 proge
nitor cells remained in the bone marrow of most mice, and spleens were almo
st 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 different
iation 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 rec
eptor-alpha (IL-2R alpha) expression. B cells transferred from normal anima
ls 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 owi
ng to a derangement in B-cell development. Because B1 cells are less depend
ent on the bone marrow, a separate mechanism for their loss is suggested.