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Publication : The Eμ enhancer region influences H chain expression and B cell fate without impacting IgVH repertoire and immune response in vivo.

First Author  Marquet M Year  2014
Journal  J Immunol Volume  193
Issue  3 Pages  1171-83
PubMed ID  24965776 Mgi Jnum  J:333216
Mgi Id  MGI:6726724 Doi  10.4049/jimmunol.1302868
Citation  Marquet M, et al. (2014) The Emu enhancer region influences H chain expression and B cell fate without impacting IgVH repertoire and immune response in vivo. J Immunol 193(3):1171-83
abstractText  The IgH intronic enhancer region Emu is a combination of both a 220-bp core enhancer element and two 310-350-bp flanking scaffold/matrix attachment regions named MARsEmu. In the mouse, deletion of the core-enhancer Emu element mainly affects VDJ recombination with minor effects on class switch recombination. We carried out endogenous deletion of the full-length Emu region (core plus MARsEmu) in the mouse genome to study VH gene repertoire and IgH expression in developing B-lineage cells. Despite a severe defect in VDJ recombination with partial blockade at the pro-B cell stage, Emu deletion (core or full length) did not affect VH gene usage. Deletion of this regulatory region induced both a decrease of pre-B cell and newly formed B cell compartments and a strong orientation toward the marginal zone B cell subset. Because Igmu H chain expression was decreased in Emu-deficient pre-B cells, we propose that modification of B cell homeostasis in deficient animals was caused by "weak" pre-B cell and BCR expression. Besides imbalances in B cell compartments, Ag-specific Ab responses were not impaired in animals carrying the Emu deletion. In addition to its role in VDJ recombination, our study points out that the full-length Emu region does not influence VH segment usage but ensures efficient Igmu-chain expression required for strong signaling through pre-B cells and newly formed BCRs and thus participates in B cell inflow and fate.
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