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

During B cell development, V-J rearrangements at the Ig heavy mu chain (IgH mu 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 mu chain expression on the rate of B cell development, purified hematopoietic stem cells (HSC) bearing a mu chain transgene or wild-type HSC were transferred into immunodeficient 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 transgenic and wild-type mice, and the production of BrdU-labeled kappa(+) and lambda(+) B cells was followed over time, These experiments suggested that early expression of the mu 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, kappa and lambda, rearrangements occurred only after the arrest of cell cycling as previously shown in wild-type mice, even when the mu chain is artificially expressed earlier in B cell development.