The functional 3'-end of immunoglobulin heavy chain variable (IGHV) genes. 2018

Linnea Thörnqvist, and Mats Ohlin
Department of Immunotechnology, Lund University, Lund, Sweden.

Inference of antibody gene repertoires using transcriptome data has emerged as an alternative approach to the complex process of sequencing of adaptive immune receptor germline gene loci. The diversity introduced during rearrangement of immunoglobulin heavy chain variable (IGHV), diversity, and joining genes has however been identified as potentially affecting inference specificity. In this study, we have addressed this issue by analysing the nucleotide composition of unmutated human immunoglobulin heavy chains-encoding transcripts, focusing on the 3ö most bases of 47 IGHV germline genes. Although transcripts derived from some of the germline genes predominately incorporated the germline encoded base even at position 320, the last base of most IGHV genes, transcripts originating in other genes presented other nucleotides to the same extent at this position. In transcripts derived from two of the germline genes, IGHV3-13*01 and IGHV4-30-2*01, the predominating nucleotide (G) was in fact not that of the gene (A). Hence, we suggest that inference of IGHV genes should be limited to bases preceding nucleotide 320, as inference beyond this would jeopardize the specificity of the inference process. The different degree of incorporation of the final base of the IGHV gene directly influences the distribution of amino acids of the ascending strand of the third complementarity determining region of the heavy chain. Thereby it influences the nature of this specificity-determining part of the antibody population. In addition, we also present data that indicate the existence of a common so far un-recognized allelic variant of IGHV3-7 that carries an A318G difference in relation to IGHV3-7*02.

UI MeSH Term Description Entries
D007135 Immunoglobulin Variable Region That region of the immunoglobulin molecule that varies in its amino acid sequence and composition, and comprises the binding site for a specific antigen. It is located at the N-terminus of the Fab fragment of the immunoglobulin. It includes hypervariable regions (COMPLEMENTARITY DETERMINING REGIONS) and framework regions. Variable Region, Ig,Variable Region, Immunoglobulin,Framework Region, Immunoglobulin,Fv Antibody Fragments,Fv Fragments,Ig Framework Region,Ig Variable Region,Immunoglobulin Framework Region,Immunoglobulin Fv Fragments,Immunoglobulin V,Antibody Fragment, Fv,Antibody Fragments, Fv,Fragment, Fv,Fragment, Fv Antibody,Fragment, Immunoglobulin Fv,Fragments, Fv,Fragments, Fv Antibody,Fragments, Immunoglobulin Fv,Framework Region, Ig,Framework Regions, Ig,Framework Regions, Immunoglobulin,Fv Antibody Fragment,Fv Fragment,Fv Fragment, Immunoglobulin,Fv Fragments, Immunoglobulin,Ig Framework Regions,Ig Variable Regions,Immunoglobulin Framework Regions,Immunoglobulin Fv Fragment,Immunoglobulin Variable Regions,Regions, Immunoglobulin Variable,Variable Regions, Ig,Variable Regions, Immunoglobulin
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D015326 Gene Rearrangement, B-Lymphocyte, Heavy Chain Ordered rearrangement of B-lymphocyte variable gene regions of the IMMUNOGLOBULIN HEAVY CHAINS, thereby contributing to antibody diversity. It occurs during the first stage of differentiation of the IMMATURE B-LYMPHOCYTES. B-Cell Heavy Chain Gene Rearrangement,B-Lymphocyte Heavy Chain Gene Rearrangement,B-Lymphocyte Mu Chain Gene Rearrangement,B Cell Heavy Chain Gene Rearrangement,B Cell Mu Chain Gene Rearrangement,B Lymphocyte Heavy Chain Gene Rearrangement,B Lymphocyte Mu Chain Gene Rearrangement
D050438 Genes, Immunoglobulin Heavy Chain Genes and gene segments encoding the IMMUNOGLOBULIN HEAVY CHAINS. Gene segments of the heavy chain genes are symbolized V (variable), D (diversity), J (joining), and C (constant). Genes, Immunoglobulin VH Germ Line,Ig Heavy Chain Genes,Immunoglobulin Heavy Chain Genes,Immunoglobulin VH Germ Line Genes

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