Early human IgH gene assembly in Epstein-Barr virus-transformed fetal B cell lines. Preferential utilization of the most JH-proximal D segment (DQ52) and two unusual VH-related rearrangements

We have analyzed the phenotypic characteristics and IgH gene rearrangements in a panel of EBV-transformed B lineage cell lines from human fetal liver and bone marrow. Some lines contained only populations of immature, Ig- Be cells, while others contained mixed populations of mature and immature B cells. The majority of identifiable IgH rearrangements involved joining of the most JH- proximal D segment, DQ52, to various JH segments, implying that DQ52 is a preferred target for initial DJH rearrangements. Three other rearrangements involving VH-related sequences were also characterized. Two involved VHDJH joining using VH3 genes, although one of these had a very unusual DJH structure. The third consisted of inverted 3' signal sequences and flanking regions of a VH4 gene appended to a JH. The mechanisms by which the later rearrangement could have occurred and its potential physiological significance are discussed.

• Publication year

  1989

• Venue

  Journal of Experimental Medicine

• Publication date

  1989-04-01

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1084/JEM.169.4.1391PMID 2538551PMCID 2189244
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Abnormalities in DNA rearrangements of immunoglobulin gene loci in precursor B cells derived from X-linked agammaglobulinemia patient and a severe combined immunodeficiency patient

  2004cited by this paper
• Sequences of proteins of immunological interest

  1991cited by this paper
• Precursor B cells transformed by Epstein-Barr virus undergo sterile plasma-cell differentiation: J-chain expression without immunoglobulin.

  1988cited by this paper
• Human immunoglobulin D segments: isolation of a new D segment and polymorphic deletion of the D1 segment.

  1988cited by this paper
• Content and organization of the human Ig VH locus: definition of three new VH families and linkage to the Ig CH locus.

  1988cited by this paper
• Unusual immunoglobulin gene rearrangement leads to replacement of recombinational signal sequences.

  1988cited by this paper
• Dispersed localization of D segments in the human immunoglobulin heavy‐chain locus.

  1988cited by this paper
• Developmentally regulated and strain-specific expression of murine VH gene families

  1988cited by this paper
• Rearrangement of IgH genes in normal thymocyte development.

  1988cited by this paper
• At least five dh genes of human immunoglobulin heavy chains are encoded in 9‐kilobase dna fragments

  1988cited by this paper
• A novel family of variable region genes of the human immunoglobulin heavy chain.

  1987cited by this paper
• Epstein‐Barr virus‐transformed human precursor B cell lines: altered growth phenotype of lines with germline or rearranged but nonexpressed heavy chain genes

  1987cited by this paper
• Physical map of the human immunoglobulin K locus and its implications for the mechanisms of VK-JK rearrangement.

  1987cited by this paper
• Progenitor and pre‐B lymphocytes transformed by epstein‐barr virus

  1987cited by this paper
• Mechanism of the t(14;18) chromosomal translocation: structural analysis of both derivative 14 and 18 reciprocal partners.

  1987cited by this paper
• Early restriction of the human antibody repertoire.

  1987cited by this paper
• Development of the primary antibody repertoire.

  1987cited by this paper
• A human monoclonal macroglobulin with specificity for alpha(2----8)- linked poly-N-acetyl neuraminic acid, the capsular polysaccharide of group B meningococci and Escherichia coli K1, which crossreacts with polynucleotides and with denatured DNA

  1986cited by this paper
• VHDJH formation and DJH replacement during pre‐B differentiation: non‐random usage of gene segments.

  1986cited by this paper
• Recombination between an expressed immunoglobulin heavy-chain gene and a germline variable gene segment in a Ly 1+ B-cell lymphoma

  1986cited by this paper
• Rearrangement of immunoglobulin heavy chain genes in human T leukaemic cells shows preferential utilization of the D segment (DQ52) nearest to the J region.

  1986cited by this paper
• A novel VH to VHDJH joining mechanism in heavy-chain-negative (null) pre-B cells results in heavy-chain production

  1986cited by this paper
• Organization and evolution of variable region genes of the human immunoglobulin heavy chain.

  1986cited by this paper
• Regulation of the assembly and expression of variable-region genes.

  1986cited by this paper
• Human B cell development. II. Subpopulations in the human fetus.

  1985cited by this paper
• Developmentally controlled expression of immunoglobulin VH genes.

  1985cited by this paper
• Direct measurement of antibody production in cell suspensions using an enzyme-linked immunosorbent assay.

  1985cited by this paper
• Preferential utilization of the most JH-proximal VH gene segments in pre-B-cell lines

  1984cited by this paper
• Epstein–Barr virus transforms precursor B cells even before immunoglobulin gene rearrangements

  1984cited by this paper
• Diversity and joining segments of mouse immunoglobulin heavy chain genes are closely linked and in the same orientation: implications for the joining mechanism.

  1983cited by this paper
• Generation and characterization of monoclonal antibodies reactive with human B lymphocytes.

  1983cited by this paper
• Structure of the human immunoglobulin μ locus: Characterization of embryonic and rearranged J and D genes

  1981cited by this paper
• Human immunoglobulin D segments encoded in tandem multigenic families

  1981cited by this paper
• Two types of somatic recombination are necessary for the generation of complete immunoglobulin heavy-chain genes

  1980cited by this paper
• Sequencing end-labeled DNA with base-specific chemical cleavages.

  1980cited by this paper
• An immunoglobulin heavy chain variable region gene is generated from three segments of DNA: VH, D and JH.

  1980cited by this paper
• Somatic generation of antibody diversity.

  1976cited by this paper

• Unmasking Human T Cell Receptor Germline Diversity: 335 Novel Alleles Identified in 47 Pangenome Reference Individuals Using the gAIRR Suite

  2025cites this paper
• Survival of the fetus: fetal B and T cell receptor repertoire development

  2017cites this paper
• Soma‐to‐germline feedback is implied by the extreme polymorphism at IGHV relative to MHC

  2015cites this paper
• Chain Cdr3 Developmental Changes in the Human Heavy

  2013cites this paper
• Etude in vivo du rôle de la région régulatrice en 3’ du locus de chaîne lourde d’immunoglobuline dans la dérégulation d’oncogènes et l’émergence de lymphomes

  2011cites this paper
• Activation of V(D)J Recombination at the IgH Chain JH Locus Occurs within a 6-Kilobase Chromatin Domain and Is Associated with Nucleosomal Remodeling1

  2006cites this paper
• Associated with Nucleosomal Remodeling 6-Kilobase Chromatin Domain and Is IgH Chain JH Locus Occurs within a Activation of V(D)J Recombination at the

  2006cites this paper
• Developmental Changes in the Human Heavy Chain CDR3

  2005cites this paper
• Expansion of a B-lymphocyte clone producing IgM auto-antibodies encoded by a somatically mutated VHI gene in the spleen of an autoimmune patient

  2004cites this paper
• Thymic Selection of the Human T Cell Receptor Vfl Repertoire in SC1D-hu Mice

  2003cites this paper
• Structure and Expression of Human Germline

  2003cites this paper
• Autoantikörper bei rheumatischen Erkrankungen

  2003cites this paper
• Immunoglobulin variable region structure and B-Cell malignancies

  2001cites this paper
• B‐cell precursors differentiated from cord blood CD34+ cells are more immature than those derived from granulocyte colony‐stimulating factor‐mobilized peripheral blood CD34+ cells

  2001cites this paper
• Altered VH6‐D‐JH repertoire in human insulin‐dependent diabetes mellitus and autoimmune idiopathic thrombocytopenic purpura

  1999cites this paper
• Characterization of the immunoglobulin light chain variable region gene expressed in multiple myeloma

  1998cites this paper
• Self-reactive antibodies (natural autoantibodies) in healthy individuals.

  1998cites this paper
• Analysis of VH genes rearranged by individual B cells in dermal infiltrates of patients with mycosis fungoides

  1997cites this paper
• Immunoglobulin heavy chain junctional diversity in young and aged humans.

  1997cites this paper
• Human Ig heavy chain CDR3 regions in adult bone marrow pre-B cells display an adult phenotype of diversity: evidence for structural selection of DH amino acid sequences.

  1997cites this paper
• Analysis of the CDR3 region of the rearranged IgH chain genes in patients with severe combined immunodeficiency and severe lymphopenia.

  1996cites this paper
• Molecular characterization of VDJ transcripts from a newborn piglet

  1996cites this paper
• Development of the immunoglobulin repertoire.

  1996cites this paper
• Rabbit DQ52 and DH gene expression in early B-cell development.

  1996cites this paper
• Population and family studies of three disease-related polymorphic genes in systemic lupus erythematosus.

  1995cites this paper
• Analysis of direct and inverted DJH rearrangements in a human Ig heavy chain transgenic minilocus.

  1995cites this paper
• Analysis of the heavy chain repertoire of human peripheral B cells using single-cell polymerase chain reaction.

  1995cites this paper
• B-cell differentiation in humans

  1995cites this paper
• Evidence for defects in V(D)J rearrangements in patients with severe combined immunodeficiency.

  1994cites this paper
• B precursor acute lymphoblastic leukemia third complementarity‐determining regions predominantly represent an unbiased recombination repertoire: Leukemic transformation frequently occurs in fetal life

  1994cites this paper
• Preferential utilization of the immature JH segment and absence of somatic mutation in the CDR3 junction of the Ig H chain gene in three X-linked severe combined immunodeficiency patients.

  1994cites this paper
• A second promoter and enhancer element within the immunoglobulin heavy chain locus

  1994cites this paper
• VH/VL gene expression in polyreactive-antibody-producing human hybridomas from the fetal B cell repertoire.

  1994cites this paper
• Overusage of Mouse DH Gene Segment, DFL16.1, Is Strain-Dependent and Determined by cis-Acting Elements

  1994influential citation
• Biased utilization of DHQ52 and JH4 gene segments in a human Ig transgenic minilocus is independent of antigenic selection.

  1994cites this paper
• The mechanism of V(D)J joining: lessons from molecular, immunological, and comparative analyses.

  1994cites this paper
• Adoptive transfer of cytotoxic T lymphocytes for the treatment of transplant-associated lymphoma.

  1993cites this paper
• Human immunoglobulin heavy-chain minilocus recombination in transgenic mice: gene-segment use in mu and gamma transcripts.

  1993cites this paper
• Structure and physical map of 64 variable segments in the 3′ 0.8–megabase region of the human immunoglobulin heavy–chain locus

  1993cites this paper
• Immunoglobulin variable region sequences of two human monoclonal antibodies directed to an onco-developmental carbohydrate antigen, lactotetraosylceramide (LcOse4Cer).

  1993cites this paper
• Mechanisms that generate human immunoglobulin diversity operate from the 8th week of gestation in fetal liver

  1993cites this paper
• Characterization of two human anti-DNA antibodies bearing the pathogenic idiotype 8.12.

  1993cites this paper
• Maintenance of CD5+ B Cells at an Early Developmental Stage by Interleukin-5: Evidence from Immunoglobulin Gene Usage in Interleukin-5 Transgenic Mice

  1993cites this paper
• Deletion mapping of Ig VH gene segments expressed in human CD5 B cell lines. JH proximity is not the sole determinant of the restricted fetal VH gene repertoire.

  1992cites this paper
• Characterization of the immunoglobulin heavy chain complementarity determining region (CDR)-III sequences from human B cell precursor acute lymphoblastic leukemia cells.

  1992influential citation
• Chromosomal organization of the heavy chain variable region gene segments comprising the human fetal antibody repertoire.

  1992cites this paper
• Developmental regulation of D beta reading frame and junctional diversity in T cell receptor-beta transcripts from human thymus.

  1992cites this paper
• The repertoire of human germline VH sequences reveals about fifty groups of VH segments with different hypervariable loops.

  1992cites this paper
• A survey of protein‐DNA interaction sites within the murine immunoglobulin heavy chain locus reveals a particularly complex pattern around the DQ52 element

  1992cites this paper
• Cellular proliferation and genetic events involved in the genesis of Burkitt lymphoma (BL) in immune compromised patients.

  1992cites this paper
• Expression of members of the immunoglobulin VH3 gene families is not restricted at the level of individual genes in human chronic lymphocytic leukemia.

  1992cites this paper
• Comparative expression of adult and fetal V gene repertoires.

  1992cites this paper
• Analysis of immunoglobulin variable region genes from human IgG anti‐DNA hybridomas

  1992cites this paper
• Simulation modeling of lymphocyte proliferation and lymphoma development in immune compromised patients

  1992influential citation
• Characterization of the Predominant T-Cell Receptor Delta (TCRδ) Rearrangements in Non-T, Non-B ALL

  1992cites this paper
• The pattern of joining (JH) gene usage in the human IgH chain is established predominantly at the B precursor cell stage.

  1992cites this paper
• Development of Human Antibody Variable Genes in Systemic Autoimmunity

  1992cites this paper
• Thymic selection of the human T cell receptor V beta repertoire in SCID- hu mice

  1992cites this paper
• Germ line transcription of the immunoglobulin heavy chain locus directs production of mu chain without VDJ.

  1992cites this paper
• Variable regions of a human anti-DNA antibody O-81 possessing lupus nephritis-associated idiotype.

  1992cites this paper
• The human cord blood antibody repertoire. Frequent usage of the VH7 gene family

  1992cites this paper
• Rearrangement and diversification of T-cell receptor delta genes in acute lymphoblastic leukemia.

  1992cites this paper
• Restricted utilization of germ‐line VH3 genes and short diverse third complementarity‐determining regions (CDR3) in human fetal B lymphocyte immunoglobulin heavy chain rearrangements

  1992cites this paper
• Emerging human B cell repertoire. Influence of developmental stage and interindividual variation.

  1992cites this paper
• Ig VH gene expression among human follicular lymphomas.

  1991cites this paper
• Organization of the T-cell receptor delta locus by deletional analysis of acute lymphoblastic leukemias and leukemic cell lines.

  1991cites this paper
• Comparison of D, JH, and junctional diversity in the fetal, adult, and aged B cell repertoires.

  1991cites this paper
• Structure and expression of human germline VH transcripts

  1991cites this paper
• Multiple mechanisms participate in the generation of diversity of human H chain CDR3 regions.

  1991cites this paper
• Antibody specificity and immunoglobulin VH utilization of human monoclonal CD5+ B cell lines

  1991cites this paper
• Specific triggering of gamma, delta T cells by K562 activates the gamma, delta T cell receptor and may regulate natural killer-like function.

  1991cites this paper
• A deletion map of the human immunoglobulin heavy chain variable region

  1991cites this paper
• Coordination of immunoglobulin DJH transcription and D-to-JH rearrangement by promoter-enhancer approximation

  1991cites this paper
• Human immunoglobulin heavy-chain variable region genes: organization, polymorphism, and expression.

  1991cites this paper
• Ig repertoire of human polyspecific antibodies and B cell ontogeny.

  1991cites this paper
• Characterization of human lymphocytes separated from fetal liver and spleen at different stages of ontogeny.

  1991cites this paper
• Restricted Ig H chain V gene usage in the human antibody response to Haemophilus influenzae type b capsular polysaccharide.

  1991cites this paper
• Interleukin-7 induces the proliferation of normal human B-cell precursors.

  1991cites this paper
• Etiological Mechanisms in Childhood Acute Lymphoblastic Leukemia

  1991cites this paper
• Complete sequence of the genes encoding the VH and VL regions of low- and high-affinity monoclonal IgM and IgA1 rheumatoid factors produced by CD5+ B cells from a rheumatoid arthritis patient.

  1991cites this paper
• Diversity of immunoglobulin heavy chain gene segment rearrangement in B lymphoblastoid cell lines from X‐linked agammaglobulinemia patients

  1991cites this paper
• The biologic significance of human natural autoimmune responses: relationship to the germline, early immune and malignant B cell variable gene repertoire.

  1990cites this paper
• Analysis of immunoglobulin and T-cell receptor gene rearrangements in human fetal bone marrow B lineage cells.

  1990cites this paper
• Human immunoglobulin VH and VK repertoire revealed by in situ hybridization.

  1990cites this paper
• Production and regulation of interleukin 6 in human B lymphoid cells

  1990cites this paper
• Lack of N regions in fetal and neonatal mouse immunoglobulin V-D-J junctional sequences

  1990cites this paper
• Restricted utilization of VH and DH genes in leukemic rabbit B cells

  1990cites this paper
• Immunoglobulin heavy chain variable region family usage is independent of tumor cell phenotype in human B lineage leukemias

  1990cites this paper
• The complete nucleotide sequences of the heavy chain variable regions of six monospecific rheumatoid factors derived from Epstein-Barr virus-transformed B cells isolated from the synovial tissue of patients with rheumatoid arthritis. Further evidence that some autoantibodies are unmutated copies of

  1990cites this paper
• Molecular analysis of 5' J region of immunoglobulin heavy chain gene in human acute leukemias.

  1990cites this paper
• Estimation of D segment usage in initial D to JH joinings in a murine immature B cell line. Preferential usage of DFL16.1, the most 5' D segment and DQ52, the most JH-proximal D segment.

  1990cites this paper
• Pathogenic anti-DNA antibodies in SLE: idiotypic families and genetic origins.

  1990cites this paper
• Preferential utilization of conserved immunoglobulin heavy chain variable gene segments during human fetal life.

  1990cites this paper
• A human anti-cardiolipin autoantibody is encoded by developementally restricted heavy and light chain variable region genes.

  1990cites this paper
• Molecular characterization of the lymphoid V(D)J recombination activity.

  1989cites this paper
• Growing human B-cell precursors in vitro: the continuing challenge.

  1989cites this paper
• Autoantibodies encoded by the most Jh-proximal human immunoglobulin heavy chain variable region gene

  1989cites this paper