Continued RAG expression in late stages of B cell development and no apparent re-induction after immunization

Models of B-cell-development in the immune system suggest that only those i mmature B cells in the bone marrow that undergo receptor editing express V( D)J-recombination-activating genes (RAGs)(1-3). Here we investigate the reg ulation of RAG expression in transgenic mice carrying a bacterial artificia l chromosome that encodes a green fluorescent. protein reporter instead of RAG2 (ref. 4). We find that the reporter is expressed in all immature B cel ls in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature beeps in bone marrow and spleen and decreases by two orders of magnitude as they acquire higher levels of surface immunoglobulin M (IgM). Once RAG expression is stopped it is not re-induced during immune response s. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate alle lic exclusion, receptor editing and tolerance.