Abstract
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
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Research Support, Non-U.S. Gov't
MeSH terms
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Alleles
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Animals
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Antibody Formation / genetics
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Antibody Formation / physiology
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B-Cell Activation Factor Receptor / metabolism
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B-Lymphocyte Subsets / metabolism
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B-Lymphocyte Subsets / physiology*
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Bone Marrow Cells / immunology
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Bone Marrow Cells / metabolism
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Bone Marrow Cells / physiology
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Cell Differentiation / genetics
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Cell Differentiation / immunology*
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Cells, Cultured
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Genes, Immunoglobulin Heavy Chain / genetics
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Genes, Immunoglobulin Heavy Chain / physiology*
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Immunoglobulin mu-Chains / genetics
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Immunoglobulin mu-Chains / metabolism
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Lectins / genetics
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Lectins / immunology
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Lectins / metabolism
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Mice
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Mice, Transgenic
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Precursor Cells, B-Lymphoid / immunology
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Precursor Cells, B-Lymphoid / metabolism
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Precursor Cells, B-Lymphoid / physiology
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Receptors, Antigen, B-Cell / genetics
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Receptors, Antigen, B-Cell / immunology*
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Receptors, Antigen, B-Cell / metabolism*
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Sialic Acid Binding Immunoglobulin-like Lectins
Substances
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B-Cell Activation Factor Receptor
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Immunoglobulin mu-Chains
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Lectins
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Receptors, Antigen, B-Cell
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Sialic Acid Binding Immunoglobulin-like Lectins
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Siglecg protein, mouse