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Early expression of Ig μ chain from a transgene significantly reduces the duration of the pro-B stage but does not affect the small pre-B stage

Abstract

During B cell development, V-J rearrangements at the Ig heavy μ chain (IgH μ chain) locus occur in early cycling precursors (pro-B stage). Subsequently, rearrangements at the Ig light (IgL) chain locus occur in late resting precursors (small pre-B stage). To study the effects of μ chain expression on the rate of B cell development, purified hematopoletic stem cells (HSC) bearing a μ chain transgene or wild-type HSC were transferred Into Immunodeficlent RAG-2-/-mice and B cell development was followed over time. In addition, cycling B cell precursors were pulse-labeled by the Injection of BrdU into transgenlc and wild-type mice, and the production of BrdU-labeled k+ and λ+ B cells was followed over time. These experiments suggested that early expression of the μ chain from the transgene significantly shortened the duration of the pro-B stage and Immediately drove the precursors to differentiate into small pre-B cells. By contrast, the presence of the transgene did not affect the small pre-B stage, where IgL rearrangements occur. Thus, k and λ rearrangements occurred only after the arrest of cell cycling as previously shown in wild-type mice, even when the μ chain is artificially expressed earlier in B cell developmen

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