Immunoglobulin variable region heptamer-nonamer recognition sequence joined to rearranged D-J segment: Implications for the immunoglobulin recombinase mechanism

Mary Stenzel-Poore, Marvin Rittenberg

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4 Citations (Scopus)

Abstract

We have found a novel immunoglobulin gene rearrangement in a murine hybridoma in which a heavy chain variable region (V(H)) heptamer-nonamer recognition sequence is joined to the diversity segment (D) through head-to-head fusion. The heptamer-nonamer recognition sequence and its adjacent 5' DNA are derived from the downstream flanking region of a germline V(H) gene. Sequence analysis indicates that this adjacent DNA is homologous to the downstream flank of V(H)108B, and it has characteristics of RNA processing that may suggest it was derived from an mRNA intermediate; these unusual features indicate that the segment is a processed gene. Because of head-to-head fusion, the recognition sequence and the flanking sequence are in opposite transcriptional polarity to D. The latter is joined correctly at its 3' border to a joining (J) gene segment. A γ1 constant region (but not μ) is located further downstream. Thus this fragment has several features common to normal immunoglobulin heavy chain gene rearrangement despite the unusual joining event involving V-D. Linkage of the V(H) heptamer-nonamer recognition sequence to D has not been observed previously. Although the recognition sequence described is inverted with respect to D and J, the endonucleolytic process that cleaved the recognition sequence at the 5' border of the heptamer before rearranging it to D was accurate. We suggest that of the three functions associated with the recombinase reaction; recognition, cutting, and ligation, only recognition and cutting may be limited to specific structures, and the ligation step may be less restricted because it is not confined to forming coding-to-coding or flank-to-flank joints. This aberrant ligation product suggests that the information leading to normal rearrangements may be found in structures that include more than the recognition sequences or coding regions alone, because the joining described here has spliced the incorrect end of a recognition sequence to a coding region to yield a non-productive recombination.

Original languageEnglish (US)
Pages (from-to)3055-3059
Number of pages5
JournalJournal of Immunology
Volume138
Issue number9
StatePublished - 1987

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VDJ Recombinases
Immunoglobulin Variable Region
Ligation
Gene Rearrangement
Immunoglobulin Heavy Chain Genes
Immunoglobulin Genes
Recombinases
Pseudogenes
DNA
Hybridomas
Genetic Recombination
Genes
Sequence Analysis
Joints
RNA
Messenger RNA

ASJC Scopus subject areas

  • Immunology

Cite this

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title = "Immunoglobulin variable region heptamer-nonamer recognition sequence joined to rearranged D-J segment: Implications for the immunoglobulin recombinase mechanism",
abstract = "We have found a novel immunoglobulin gene rearrangement in a murine hybridoma in which a heavy chain variable region (V(H)) heptamer-nonamer recognition sequence is joined to the diversity segment (D) through head-to-head fusion. The heptamer-nonamer recognition sequence and its adjacent 5' DNA are derived from the downstream flanking region of a germline V(H) gene. Sequence analysis indicates that this adjacent DNA is homologous to the downstream flank of V(H)108B, and it has characteristics of RNA processing that may suggest it was derived from an mRNA intermediate; these unusual features indicate that the segment is a processed gene. Because of head-to-head fusion, the recognition sequence and the flanking sequence are in opposite transcriptional polarity to D. The latter is joined correctly at its 3' border to a joining (J) gene segment. A γ1 constant region (but not μ) is located further downstream. Thus this fragment has several features common to normal immunoglobulin heavy chain gene rearrangement despite the unusual joining event involving V-D. Linkage of the V(H) heptamer-nonamer recognition sequence to D has not been observed previously. Although the recognition sequence described is inverted with respect to D and J, the endonucleolytic process that cleaved the recognition sequence at the 5' border of the heptamer before rearranging it to D was accurate. We suggest that of the three functions associated with the recombinase reaction; recognition, cutting, and ligation, only recognition and cutting may be limited to specific structures, and the ligation step may be less restricted because it is not confined to forming coding-to-coding or flank-to-flank joints. This aberrant ligation product suggests that the information leading to normal rearrangements may be found in structures that include more than the recognition sequences or coding regions alone, because the joining described here has spliced the incorrect end of a recognition sequence to a coding region to yield a non-productive recombination.",
author = "Mary Stenzel-Poore and Marvin Rittenberg",
year = "1987",
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volume = "138",
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T1 - Immunoglobulin variable region heptamer-nonamer recognition sequence joined to rearranged D-J segment

T2 - Implications for the immunoglobulin recombinase mechanism

AU - Stenzel-Poore, Mary

AU - Rittenberg, Marvin

PY - 1987

Y1 - 1987

N2 - We have found a novel immunoglobulin gene rearrangement in a murine hybridoma in which a heavy chain variable region (V(H)) heptamer-nonamer recognition sequence is joined to the diversity segment (D) through head-to-head fusion. The heptamer-nonamer recognition sequence and its adjacent 5' DNA are derived from the downstream flanking region of a germline V(H) gene. Sequence analysis indicates that this adjacent DNA is homologous to the downstream flank of V(H)108B, and it has characteristics of RNA processing that may suggest it was derived from an mRNA intermediate; these unusual features indicate that the segment is a processed gene. Because of head-to-head fusion, the recognition sequence and the flanking sequence are in opposite transcriptional polarity to D. The latter is joined correctly at its 3' border to a joining (J) gene segment. A γ1 constant region (but not μ) is located further downstream. Thus this fragment has several features common to normal immunoglobulin heavy chain gene rearrangement despite the unusual joining event involving V-D. Linkage of the V(H) heptamer-nonamer recognition sequence to D has not been observed previously. Although the recognition sequence described is inverted with respect to D and J, the endonucleolytic process that cleaved the recognition sequence at the 5' border of the heptamer before rearranging it to D was accurate. We suggest that of the three functions associated with the recombinase reaction; recognition, cutting, and ligation, only recognition and cutting may be limited to specific structures, and the ligation step may be less restricted because it is not confined to forming coding-to-coding or flank-to-flank joints. This aberrant ligation product suggests that the information leading to normal rearrangements may be found in structures that include more than the recognition sequences or coding regions alone, because the joining described here has spliced the incorrect end of a recognition sequence to a coding region to yield a non-productive recombination.

AB - We have found a novel immunoglobulin gene rearrangement in a murine hybridoma in which a heavy chain variable region (V(H)) heptamer-nonamer recognition sequence is joined to the diversity segment (D) through head-to-head fusion. The heptamer-nonamer recognition sequence and its adjacent 5' DNA are derived from the downstream flanking region of a germline V(H) gene. Sequence analysis indicates that this adjacent DNA is homologous to the downstream flank of V(H)108B, and it has characteristics of RNA processing that may suggest it was derived from an mRNA intermediate; these unusual features indicate that the segment is a processed gene. Because of head-to-head fusion, the recognition sequence and the flanking sequence are in opposite transcriptional polarity to D. The latter is joined correctly at its 3' border to a joining (J) gene segment. A γ1 constant region (but not μ) is located further downstream. Thus this fragment has several features common to normal immunoglobulin heavy chain gene rearrangement despite the unusual joining event involving V-D. Linkage of the V(H) heptamer-nonamer recognition sequence to D has not been observed previously. Although the recognition sequence described is inverted with respect to D and J, the endonucleolytic process that cleaved the recognition sequence at the 5' border of the heptamer before rearranging it to D was accurate. We suggest that of the three functions associated with the recombinase reaction; recognition, cutting, and ligation, only recognition and cutting may be limited to specific structures, and the ligation step may be less restricted because it is not confined to forming coding-to-coding or flank-to-flank joints. This aberrant ligation product suggests that the information leading to normal rearrangements may be found in structures that include more than the recognition sequences or coding regions alone, because the joining described here has spliced the incorrect end of a recognition sequence to a coding region to yield a non-productive recombination.

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