Combination of 3' and 5' IgH regulatory elements mimics the B-specific endogenous expression pattern of IgH genes from pro-B cells to mature B cells in a transgenic mouse model

摘要

To ensure the B cell differentiation stage specificity of the intronic Eμ element and of the locus control region (LCR) that lies downstream of the IgH chain locus, we generated transgenic mice harboring a V_H promoter-GFP reporter gene linked to the 3'LCR region and the Eμ element. By flow cytometry, GFP~+ lymphocytes were observed amongst pro-B cells (B220~+CD43~+CD117~+) and at all stages of differentiation up to mature B cells (B220~+IgM~+IgD~+). Expression was strictly confined to cells committed to the B lymphocyte lineage as judged by the lack of GFP~+Thy1,2~+ cells (T lymphocytes) and GFP~+B220~-CD117~+CD43~+ cells (uncommitted lymphohematopoietic progenitors). Therefore, the Eμ-GFP-3'LCR transgene is not expressed by hematopoietic stem cells, begins its expression in pro-B cells and is specifically active at all stages of B cell maturation. The combination of 3' and 5' IgH regulatory elements thus appears as a potentially useful cassette in transgenes that require a stringent and early B lineage-specific expression.