Control of the sizes and contents of precursor B cell repertoires in bone marrow. 1997

F Melchers
Basel Institute for Immunology, Switzerland.

Ordered rearrangements of immunoglobulin (Ig) gene loci, first as DH to JH, then as VH to DHJH, and finally as VL to JL segment-specific recombinations occur 'in-frame' and 'out-of-frame'. 'In-frame' rearrangements lead to the expression of truncated DHJH-microC proteins and to microH chains. These H chain proteins have two major effects on precursor B cells. They suppress (as DJC mu proteins) or enhance (as full microH chain) the proliferation of precursor cells at the point where these precursors express these proteins. At the same time, they signal allelic exclusion of the microH chain alleles, so that VH to DHJH rearrangement at the second allele is suppressed. Regulation of precursor B cell proliferation and H chain allelic exclusion is mediated by a pre-B cell receptor that is composed of the microH chains and a surrogate L chain. This surrogate L chain is made up of two proteins encoded by the Vpre-B and lambda 5 genes that are expressed only at the early precursor cell stages just before and when H chain genes are first expressed. They are not found in later B cell development, when L chains are expressed, nor in any other cell of the body tested so far. The physiological roles of surrogate L chain and of the pre-B receptor have been clarified by generating mutant mice in which the lambda 5 gene has been inactivated by targeted disruption. Molecular mechanisms and cellular developments, by which the pre-B receptor controls proliferation and allelic exclusion, are discussed.

UI MeSH Term Description Entries
D007146 Immunoglobulin lambda-Chains One of the types of light chain subunits of the immunoglobulins with a molecular weight of approximately 22 kDa. Ig lambda Chains,Immunoglobulins, lambda-Chain,Immunoglobulin lambda-Chain,lambda-1-Immunoglobulin,lambda-2-Immunoglobulin,lambda-Chain Immunoglobulins,lambda-Immunoglobulin Light Chain,lambda-Immunoglobulin Light Chains,lambda-x Immunoglobulin,Chains, Ig lambda,Chains, lambda-Immunoglobulin Light,Immunoglobulin lambda Chain,Immunoglobulin lambda Chains,Immunoglobulin, lambda-x,Immunoglobulins, lambda Chain,Light Chain, lambda-Immunoglobulin,Light Chains, lambda-Immunoglobulin,lambda 1 Immunoglobulin,lambda 2 Immunoglobulin,lambda Chain Immunoglobulins,lambda Chains, Ig,lambda Immunoglobulin Light Chain,lambda Immunoglobulin Light Chains,lambda x Immunoglobulin,lambda-Chain, Immunoglobulin,lambda-Chains, Immunoglobulin
D007148 Immunoglobulin mu-Chains The class of heavy chains found in IMMUNOGLOBULIN M. They have a molecular weight of approximately 72 kDa and they contain about 57 amino acid residues arranged in five domains and have more oligosaccharide branches and a higher carbohydrate content than the heavy chains of IMMUNOGLOBULIN G. Ig mu Chains,Immunoglobulins, mu-Chain,Immunoglobulin mu-Chain,mu Immunoglobulin Heavy Chain,mu Immunoglobulin Heavy Chains,mu-Chain Immunoglobulins,Chains, Ig mu,Immunoglobulin mu Chain,Immunoglobulin mu Chains,Immunoglobulins, mu Chain,mu Chain Immunoglobulins,mu Chains, Ig,mu-Chain, Immunoglobulin,mu-Chains, Immunoglobulin
D009687 Nuclear Proteins Proteins found in the nucleus of a cell. Do not confuse with NUCLEOPROTEINS which are proteins conjugated with nucleic acids, that are not necessarily present in the nucleus. Nucleolar Protein,Nucleolar Proteins,Nuclear Protein,Protein, Nuclear,Protein, Nucleolar,Proteins, Nuclear,Proteins, Nucleolar
D011506 Proteins Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein. Gene Products, Protein,Gene Proteins,Protein,Protein Gene Products,Proteins, Gene
D011947 Receptors, Antigen, B-Cell IMMUNOGLOBULINS on the surface of B-LYMPHOCYTES. Their MESSENGER RNA contains an EXON with a membrane spanning sequence, producing immunoglobulins in the form of type I transmembrane proteins as opposed to secreted immunoglobulins (ANTIBODIES) which do not contain the membrane spanning segment. Antigen Receptors, B-Cell,B-Cell Antigen Receptor,B-Cell Antigen Receptors,Surface Immunoglobulin,Immunoglobulins, Membrane-Bound,Immunoglobulins, Surface,Membrane Bound Immunoglobulin,Membrane-Bound Immunoglobulins,Receptors, Antigen, B Cell,Surface Immunoglobulins,Antigen Receptor, B-Cell,Antigen Receptors, B Cell,B Cell Antigen Receptor,B Cell Antigen Receptors,Bound Immunoglobulin, Membrane,Immunoglobulin, Membrane Bound,Immunoglobulin, Surface,Immunoglobulins, Membrane Bound,Membrane Bound Immunoglobulins,Receptor, B-Cell Antigen,Receptors, B-Cell Antigen
D001854 Bone Marrow Cells Cells contained in the bone marrow including fat cells (see ADIPOCYTES); STROMAL CELLS; MEGAKARYOCYTES; and the immediate precursors of most blood cells. Bone Marrow Cell,Cell, Bone Marrow,Cells, Bone Marrow,Marrow Cell, Bone,Marrow Cells, Bone
D002454 Cell Differentiation Progressive restriction of the developmental potential and increasing specialization of function that leads to the formation of specialized cells, tissues, and organs. Differentiation, Cell,Cell Differentiations,Differentiations, Cell
D004268 DNA-Binding Proteins Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases. DNA Helix Destabilizing Proteins,DNA-Binding Protein,Single-Stranded DNA Binding Proteins,DNA Binding Protein,DNA Single-Stranded Binding Protein,SS DNA BP,Single-Stranded DNA-Binding Protein,Binding Protein, DNA,DNA Binding Proteins,DNA Single Stranded Binding Protein,DNA-Binding Protein, Single-Stranded,Protein, DNA-Binding,Single Stranded DNA Binding Protein,Single Stranded DNA Binding Proteins
D005803 Genes, Immunoglobulin Genes encoding the different subunits of the IMMUNOGLOBULINS, for example the IMMUNOGLOBULIN LIGHT CHAIN GENES and the IMMUNOGLOBULIN HEAVY CHAIN GENES. The heavy and light immunoglobulin genes are present as gene segments in the germline cells. The completed genes are created when the segments are shuffled and assembled (B-LYMPHOCYTE GENE REARRANGEMENT) during B-LYMPHOCYTE maturation. The gene segments of the human light and heavy chain germline genes are symbolized V (variable), J (joining) and C (constant). The heavy chain germline genes have an additional segment D (diversity). Genes, Ig,Immunoglobulin Genes,Gene, Ig,Gene, Immunoglobulin,Ig Gene,Ig Genes,Immunoglobulin Gene
D006412 Hematopoietic Stem Cells Progenitor cells from which all blood cells derived. They are found primarily in the bone marrow and also in small numbers in the peripheral blood. Colony-Forming Units, Hematopoietic,Progenitor Cells, Hematopoietic,Stem Cells, Hematopoietic,Hematopoietic Progenitor Cells,Cell, Hematopoietic Progenitor,Cell, Hematopoietic Stem,Cells, Hematopoietic Progenitor,Cells, Hematopoietic Stem,Colony Forming Units, Hematopoietic,Colony-Forming Unit, Hematopoietic,Hematopoietic Colony-Forming Unit,Hematopoietic Colony-Forming Units,Hematopoietic Progenitor Cell,Hematopoietic Stem Cell,Progenitor Cell, Hematopoietic,Stem Cell, Hematopoietic,Unit, Hematopoietic Colony-Forming,Units, Hematopoietic Colony-Forming

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