To study homeostasis of peripheral B lymphocytes in the absence of B cell i
nflux from the bone marrow, we generated a mouse mutant in which the recomb
ination-activating gene (RAG)-2 can be inducibly deleted. When RAG-2 was de
leted at the age of 8-10 wk, splenic naive follicular B cells were graduall
y lost over a year of observation, with a half-life of similar to4.5 mo. By
contrast, the pool of marginal zone B cells in the spleen and of B-1 cells
in the peritoneal cavity were kept at normal level. In lymph nodes, simila
r to 90% of the B cells were lost within 4 mo, and B cell numbers remained
constant thereafter. Mice in which RAG-2 was deleted at birth maintained a
small population of activated B cells with an increased proportion of margi
nal zone B cells. Additionally, an increase of the pool of IgM secreting ce
lls and B-1a cells was observed.