A hypomorphic IgH-chain allele affects development of B-cell subsets and favours receptor editing

EMBO J. 2011 May 27;30(13):2705-18. doi: 10.1038/emboj.2011.168.


The quality and quantity of BCR signals impact on cell fate decisions of B lymphocytes. Here, we describe novel gene-targeted mice, which in the context of normal VDJ recombination show hypomorphic expression of immunoglobulin μ heavy chain (μHC) mRNA levels and hence lower pre-BCR and BCR levels. Hypomorphic expression of μHC leads to augmented selection processes at all stages of B-cell development, noticeably at the expansion of pre-B cells, the positive selection of immature B lymphocytes in the bone marrow and the selection of the follicular (FO), marginal zone (MZ) and B1 B-lymphocyte compartment in peripheral lymphoid organs. Immature as well as mature FO and MZ B lymphocytes in the peripheral lymphoid organs express lower levels of the receptor for B-cell activating factor (BAFF). In addition, hypomorphic expression of the BCR favours receptor editing. Together, our results highlight the critical importance of pre-BCR and BCR receptor levels for the normal development of B-lymphocyte subpopulations in the context of intact VDJ recombination and a diverse antibody repertoire.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alleles
  • Animals
  • Antibody Formation / genetics
  • Antibody Formation / physiology
  • B-Cell Activation Factor Receptor / metabolism
  • B-Lymphocyte Subsets / metabolism
  • B-Lymphocyte Subsets / physiology*
  • Bone Marrow Cells / immunology
  • Bone Marrow Cells / metabolism
  • Bone Marrow Cells / physiology
  • Cell Differentiation / genetics
  • Cell Differentiation / immunology*
  • Cells, Cultured
  • Genes, Immunoglobulin Heavy Chain / genetics
  • Genes, Immunoglobulin Heavy Chain / physiology*
  • Immunoglobulin mu-Chains / genetics
  • Immunoglobulin mu-Chains / metabolism
  • Lectins / genetics
  • Lectins / immunology
  • Lectins / metabolism
  • Mice
  • Mice, Transgenic
  • Precursor Cells, B-Lymphoid / immunology
  • Precursor Cells, B-Lymphoid / metabolism
  • Precursor Cells, B-Lymphoid / physiology
  • Receptors, Antigen, B-Cell / genetics
  • Receptors, Antigen, B-Cell / immunology*
  • Receptors, Antigen, B-Cell / metabolism*
  • Sialic Acid Binding Immunoglobulin-like Lectins


  • B-Cell Activation Factor Receptor
  • Immunoglobulin mu-Chains
  • Lectins
  • Receptors, Antigen, B-Cell
  • Sialic Acid Binding Immunoglobulin-like Lectins
  • Siglecg protein, mouse