Ordered rearrangement of immunoglobulin heavy chain variable region segments
Open accessAbstract
The immunoglobulin heavy chain variable region is encoded as three separate libraries of elements in germ-line DNA: VH, D and JH. To examine the order and regulation of their joining, we have developed assays that distinguish their various combinations and have used the assays to study tumor cell analogs of B-lymphoid cells as well as normal B-lymphoid cells. Abelson murine leukemia virus (A-MuLV) transformed fetal liver cells - the most primitive B-lymphoid cell analog available for analysis - generally had DJH rearrangements at both JH loci. These lines continued DNA rearrangement in culture, in most cases by joining a VH gene segment to an existing DJH complex with the concomitant deletion of intervening DNA sequences. None of these lines or their progeny showed evidence of VHD or DD rearrangements. Heavy chain-producing tumor lines, representing more mature stages of the B-cell pathway, and normal B-lymphocytes had either two VHDJH rearrangements or a VHDJH plus a DJH rearrangement at their two heavy chain loci; they also showed no evidence of VHD or DD rearrangements. These results support an ordered mechanism of variable gene assembly during B-cell differentiation in which D-to-JH rearrangements generally occur first and on both chromosomes followed by VH-to-DJH rearrangements, with both types of joining processes occurring by intrachromosomal deletion. The high percentage of JH alleles remaining in the DJH configuration in heavy chain-producing lines and, especially, in normal B-lymphocytes supports a regulated mechanism of heavy chain allelic exclusion in which a VHDJH rearrangement, if productive, prevents an additional VH-to-DJH rearrangement.
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A v-Abl transformed B cell progenitor line, 38B9, and several human B cell cancer lines were sensitive to TRIM33 knockdown.
“Furthermore, a v-Abl transformed B cell progenitor line, 38B9 (Alt et al., 1984), and several human B cell cancer lines were also sensitive to TRIM33 knockdown”
From The transcriptional cofactor TRIM33 prevents apoptosis in B lymphoblastic leukemia by deactivating a single enhancer (2015) · cites this paper as Alt et al., 1984
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“Furthermore, a v-Abl transformed B cell progenitor line, 38B9 (Alt et al., 1984), and several human B cell cancer lines were also sensitive to TRIM33 knockdown (Figure 1C and Figure 1—figure supplement 1).”
BackgroundMethodInfluential
- Authors
- Alt, F. W., Yancopoulos, G. D., Blackwell, T. K., Wood, C., Thomas, E., Boss, M., Coffman, R., Rosenberg, N., Tonegawa, S., & Baltimore, D.
- Affiliations
- Whitehead Institute for Biomedical Research (US)
- Venue
- The EMBO Journal
- Published
- 1984-06-01
- Volume
- 3
- Issue
- 6
- Pages
- 1209-1219
- ISSN
- 0261-4189 (ISSN-L)
- 1460-2075
- PMC
- PMC557501
- OpenAlex
- W1747312855
- Cited by
- 733
- References
- 28
- Citations by year
- 2026: 3 · 2025: 8 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 4 · 2020: 6 · 2019: 15 · 2018: 13 · 2017: 13 · 2016: 4 · 2015: 14 · 2014: 20 · 2013: 8 · 2012: 11
- FWCI
- 20.18
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The EMBO Journal (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Searle Scholars Program
- National Institutes of Health
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › DNA Repair Mechanisms
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- immunoglobulin heavy chain variable region, V(D)J recombination, allelic exclusion, B cell differentiation, fetal liver cells
- MeSH terms
- Abelson murine leukemia virus, Alleles, Animals, B-Lymphocytes, Base Sequence, Bone Marrow, Cell Line, Cell Transformation, Neoplastic, Cloning, Molecular, DNA Restriction Enzymes, Genes, Humans, Immunoglobulin Variable Region, Immunoglobulin Heavy Chains, Immunoglobulin kappa-Chains, Immunoglobulin Light Chains, Liver, Lymphoma, Plasmacytoma, Mice
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