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

J Immunol. 2014 Aug 1;193(3):1171-83. doi: 10.4049/jimmunol.1302868. Epub 2014 Jun 25.


The IgH intronic enhancer region Eμ is a combination of both a 220-bp core enhancer element and two 310-350-bp flanking scaffold/matrix attachment regions named MARsEμ. In the mouse, deletion of the core-enhancer Eμ element mainly affects VDJ recombination with minor effects on class switch recombination. We carried out endogenous deletion of the full-length Eμ region (core plus MARsEμ) 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, Eμ 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 Igμ H chain expression was decreased in Eμ-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 Eμ deletion. In addition to its role in VDJ recombination, our study points out that the full-length Eμ region does not influence VH segment usage but ensures efficient Igμ-chain expression required for strong signaling through pre-B cells and newly formed BCRs and thus participates in B cell inflow and fate.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • B-Lymphocyte Subsets / cytology
  • B-Lymphocyte Subsets / immunology*
  • B-Lymphocyte Subsets / metabolism
  • Cell Movement / genetics
  • Cell Movement / immunology
  • Enhancer Elements, Genetic / immunology*
  • Gene Deletion
  • Gene Expression Regulation / immunology*
  • Genes, Immunoglobulin Heavy Chain / immunology*
  • Immunoglobulin Class Switching / genetics
  • Immunoglobulin Variable Region / genetics*
  • Immunoglobulin mu-Chains / biosynthesis
  • Immunoglobulin mu-Chains / genetics*
  • Mice
  • Mice, 129 Strain
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Models, Animal
  • Random Allocation
  • Receptors, Antigen, B-Cell / biosynthesis
  • Receptors, Antigen, B-Cell / genetics
  • Signal Transduction / genetics
  • Signal Transduction / immunology
  • Stem Cells / cytology
  • Stem Cells / immunology
  • Stem Cells / metabolism
  • V(D)J Recombination / genetics
  • V(D)J Recombination / immunology


  • Immunoglobulin Variable Region
  • Immunoglobulin mu-Chains
  • Receptors, Antigen, B-Cell