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.
Arakawa
H
H
Basel Institute for Immunology, Switzerland.
Takeda
S
S
D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology*; D002454:Cell Differentiation; D015870:Gene Expression; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D018380:Hematopoietic Stem Cell Transplantation; D006412:Hematopoietic Stem Cells / Q000276:immunology*; D007075:Immunoglobulin M / Q000378:metabolism; D007148:Immunoglobulin mu-Chains / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D013997:Time Factors
D007075:Immunoglobulin M; D007148:Immunoglobulin mu-Chains; D011947:Receptors, Antigen, B-Cell