Abstract
Models of B-cell development in the immune system suggest that only those immature B cells in the bone marrow that undergo receptor editing express V (D)J -recombination-activating genes (RAGs)1,2,3. Here we investigate the regulation of RAG expression in transgenic mice carrying a bacterial artificial chromosome that encodes a green fluorescent protein reporter instead of RAG2 (ref. 4). We find that the reporter is expressed in all immature B cells in the bone marrow and spleen. Endogenous RAG messenger RNA is expressed in immature B cells 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 responses. Our findings may help to reconcile a series of apparently contradictory observations, and suggest a new model for the mechanisms that regulate allelic exclusion, receptor editing and tolerance.
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Acknowledgements
We thank R. Monroe, C. Seidel and F. Alt for discussing unpublished data; P. Cortes for discussion and anti-RAG2 polyclonal antibodies; N. Heintz and W. Yang for help with BAC technology; and F. Isdell and M. Genova for cell sorting. W.Y. was supported by the NIH, the Surdna Foundation and the William Randolph Hearst Foundation. This work was funded in part by grants from the NIH to M.C.N.
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Yu, W., Nagaoka, H., Jankovic, M. et al. Continued RAG expression in late stages of B cell development and no apparent re-induction after immunizion. Nature 400, 682–687 (1999). https://doi.org/10.1038/23287
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DOI: https://doi.org/10.1038/23287
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