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  1. Article ; Online: Why does somatic hypermutation by AID require transcription of its target genes?

    Storb, Ursula

    Advances in immunology

    2014  Volume 122, Page(s) 253–277

    Abstract: In this review, I discuss the currently available experimental evidence concerning the molecular interactions of the activation-induced cytidine deaminase (AID) with transcription of its target genes. The basic question that underlies the transcription ... ...

    Abstract In this review, I discuss the currently available experimental evidence concerning the molecular interactions of the activation-induced cytidine deaminase (AID) with transcription of its target genes. The basic question that underlies the transcription relationship is how the process of somatic hypermutation of Ig genes can be restricted to their variable (V) regions. This hallmark of SHM assures that high affinity antibodies can be created while the biological functions of their constant (C) region are undisturbed. I present a revised model of AID function in somatic hypermutation (SHM): In a B cell that produces AID protein and undergoes mutation of the V regions of the expressed Ig heavy and light chain genes, only some of the transcription complexes initiating at the active V-region promoters are associated with AID. When AID travels with the elongating RNA polymerase (pol), it attracts proteins that cause the pausing/stalling of pol and termination of transcription, followed by termination of SHM. This differential AID loading model would allow the mutating B cell to continue producing full-length Ig proteins that are required to avoid apoptosis by permitting the cell to assemble functional B cell receptors.
    MeSH term(s) Animals ; B-Lymphocyte Subsets/immunology ; Cytidine Deaminase/biosynthesis ; Cytidine Deaminase/deficiency ; Cytidine Deaminase/physiology ; Gene Targeting/methods ; Humans ; Immunoglobulin Heavy Chains/genetics ; Immunoglobulin Light Chains/genetics ; Lymphocyte Activation/genetics ; Lymphocyte Activation/immunology ; Mice ; Mutation ; Somatic Hypermutation, Immunoglobulin/genetics ; Somatic Hypermutation, Immunoglobulin/immunology ; Transcriptional Activation/genetics ; Transcriptional Activation/immunology
    Chemical Substances Immunoglobulin Heavy Chains ; Immunoglobulin Light Chains ; AICDA (activation-induced cytidine deaminase) (EC 3.5.4.-) ; Cytidine Deaminase (EC 3.5.4.5)
    Language English
    Publishing date 2014
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 80226-8
    ISSN 1557-8445 ; 0065-2776
    ISSN (online) 1557-8445
    ISSN 0065-2776
    DOI 10.1016/B978-0-12-800267-4.00007-9
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  2. Article ; Online: Growth of Coal Mining Operations in the Elk River Valley (Canada) Linked to Increasing Solute Transport of Se, NO

    Storb, Meryl B / Bussell, Ashley M / Caldwell Eldridge, Sara L / Hirsch, Robert M / Schmidt, Travis S

    Environmental science & technology

    2023  Volume 57, Issue 45, Page(s) 17465–17480

    Abstract: Koocanusa Reservoir (KOC) is a waterbody that spans the United States (U.S.) and Canadian border ...

    Abstract Koocanusa Reservoir (KOC) is a waterbody that spans the United States (U.S.) and Canadian border. Increasing concentrations of total selenium (Se), nitrate + nitrite (NO
    MeSH term(s) Coal Mining ; Selenium/analysis ; Canada ; Nitrites ; Environmental Monitoring ; Rivers ; Water Pollutants, Chemical/analysis
    Chemical Substances Selenium (H6241UJ22B) ; Nitrites ; Water Pollutants, Chemical
    Language English
    Publishing date 2023-11-03
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
    ISSN 1520-5851
    ISSN (online) 1520-5851
    DOI 10.1021/acs.est.3c05090
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  3. Article: DNA polymerases in immunity: profiting from errors.

    Storb, U

    Nature immunology

    2001  Volume 2, Issue 6, Page(s) 484–485

    MeSH term(s) Amino Acid Sequence ; Animals ; DNA-Directed DNA Polymerase/immunology ; DNA-Directed DNA Polymerase/metabolism ; Genes, Immunoglobulin ; Humans ; Mutation
    Chemical Substances DNA-Directed DNA Polymerase (EC 2.7.7.7) ; Rad30 protein (EC 2.7.7.7)
    Language English
    Publishing date 2001-06
    Publishing country United States
    Document type Comment ; News
    ZDB-ID 2016987-5
    ISSN 1529-2916 ; 1529-2908
    ISSN (online) 1529-2916
    ISSN 1529-2908
    DOI 10.1038/88673
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  4. Article ; Online: Comparison of reduced intensity and nonmyeloablative conditioning for adults with acute myeloid leukemia undergoing allogeneic hematopoietic cell transplantation in first or second remission.

    Walter, Roland B / Sandmaier, Brenda M / Othus, Megan / Orvain, Corentin / Rodríguez-Arbolí, Eduardo / Oshima, Masumi U / Schoch, Gary / Davis, Chris / Joachim Deeg, H / Storb, Rainer

    Bone marrow transplantation

    2022  Volume 58, Issue 4, Page(s) 377–385

    Abstract: Reduced intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning regimens have expanded use of allogeneic hematopoietic cell transplantation (HCT) in AML to include older and medically less-fit patients, but relative efficacies and toxicities ...

    Abstract Reduced intensity conditioning (RIC) and nonmyeloablative (NMA) conditioning regimens have expanded use of allogeneic hematopoietic cell transplantation (HCT) in AML to include older and medically less-fit patients, but relative efficacies and toxicities remain poorly defined. Here, we analyzed outcomes from 343 adults transplanted in remission after RIC (n = 137) or NMA (n = 206) conditioning between 2006 and 2021. The characteristics of RIC and NMA HCT patients were similar except that RIC patients were younger and their time between most recent remission achievement and allografting was shorter. There were no significant differences in relapse risk, relapse-free survival (RFS), overall survival (OS), and non-relapse mortality (NRM) between RIC and NMA HCT patients, both overall (relapse: hazard ratio [HR] = 0.80, P = 0.27; RFS: HR = 0.93, P = 0.61; OS: HR = 0.93, P = 0.66; NRM: HR = 1.13, P = 0.59) and when patients were stratified by pre-HCT measurable residual disease (MRD) status. After multivariable adjustment, there was no statistically significant association between conditioning intensity and relapse (HR = 0.69, P = 0.088), RFS (HR = 0.86, P = 0.37), OS (HR = 0.89, P = 0.49), or NRM (HR = 1.37, P = 0.19). In this non-randomized cohort of adults undergoing allografting for AML in first or second remission at our center, we could not detect statistically significant differences in outcomes between those assigned to RIC and those assigned to NMA conditioning.
    MeSH term(s) Adult ; Humans ; Leukemia, Myeloid, Acute/therapy ; Hematopoietic Stem Cell Transplantation ; Transplantation, Homologous ; Recurrence ; Transplantation Conditioning ; Retrospective Studies
    Language English
    Publishing date 2022-12-28
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 632854-4
    ISSN 1476-5365 ; 0268-3369 ; 0951-3078
    ISSN (online) 1476-5365
    ISSN 0268-3369 ; 0951-3078
    DOI 10.1038/s41409-022-01909-x
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  5. Article: Progress in understanding the mechanism and consequences of somatic hypermutation.

    Storb, U

    Immunological reviews

    1998  Volume 162, Page(s) 5–11

    MeSH term(s) Animals ; Antibody Diversity/genetics ; Evolution, Molecular ; Genes, Immunoglobulin ; Humans ; Leukemia, B-Cell/genetics ; Leukemia, B-Cell/immunology ; Lymphoma, B-Cell/genetics ; Lymphoma, B-Cell/immunology ; Mutation
    Language English
    Publishing date 1998-04
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/j.1600-065x.1998.tb01424.x
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  6. Article: The molecular basis of somatic hypermutation of immunoglobulin genes.

    Storb, U

    Current opinion in immunology

    1996  Volume 8, Issue 2, Page(s) 206–214

    Abstract: Somatic hypermutation amplifies the variable region repertoire of immunoglobulin genes. Recent experimental evidence has thrown light on various molecular models of somatic hypermutation. A link between somatic hypermutation and transcription coupled DNA ...

    Abstract Somatic hypermutation amplifies the variable region repertoire of immunoglobulin genes. Recent experimental evidence has thrown light on various molecular models of somatic hypermutation. A link between somatic hypermutation and transcription coupled DNA repair is shaping up.
    MeSH term(s) Animals ; Genes, Immunoglobulin/genetics ; Models, Genetic ; Mutation/immunology
    Language English
    Publishing date 1996-04
    Publishing country England
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 1035767-1
    ISSN 1879-0372 ; 0952-7915
    ISSN (online) 1879-0372
    ISSN 0952-7915
    DOI 10.1016/s0952-7915(96)80059-8
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  7. Article: Steps in the generation of autoantibodies.

    Storb, U

    Annals of the New York Academy of Sciences

    1993  Volume 681, Page(s) 29–32

    MeSH term(s) Animals ; Autoantibodies/biosynthesis ; Autoimmunity ; B-Lymphocytes/immunology ; Humans ; Immune Tolerance ; Immunologic Memory ; T-Lymphocytes/immunology
    Chemical Substances Autoantibodies
    Language English
    Publishing date 1993-06-21
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 211003-9
    ISSN 1749-6632 ; 0077-8923
    ISSN (online) 1749-6632
    ISSN 0077-8923
    DOI 10.1111/j.1749-6632.1993.tb22866.x
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  8. Article: The published data.

    Storb, U

    Immunological reviews

    1990  Volume 115, Page(s) 253–7; discussion 258–60

    MeSH term(s) Animals ; Antibody Diversity/genetics ; B-Lymphocytes/immunology ; Gene Rearrangement, B-Lymphocyte/genetics ; Gene Rearrangement, B-Lymphocyte/immunology ; Genes, Immunoglobulin ; Mice ; Mice, Transgenic
    Language English
    Publishing date 1990-06
    Publishing country England
    Document type Journal Article ; Review
    ZDB-ID 391796-4
    ISSN 1600-065X ; 0105-2896
    ISSN (online) 1600-065X
    ISSN 0105-2896
    DOI 10.1111/j.1600-065x.1990.tb00798.x
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  9. Article ; Online: Ssm1b expression and function in germ cells of adult mice and in early embryos.

    Ratnam, Sarayu / Bozek, Grazyna / Martin, Terence / Gallagher, Shannon J / Payne, Christopher J / Storb, Ursula

    Molecular reproduction and development

    2017  Volume 84, Issue 7, Page(s) 596–613

    Abstract: Ssm1b (Strain-specific modifier of DNA methylation 1b) is a Krüppel-associated box (KRAB) zinc finger gene that promotes CpG methylation in the mouse transgene HRD (Heavy chain enhancer, rearrangement by deletion). We report here that Ssm1b expression ... ...

    Abstract Ssm1b (Strain-specific modifier of DNA methylation 1b) is a Krüppel-associated box (KRAB) zinc finger gene that promotes CpG methylation in the mouse transgene HRD (Heavy chain enhancer, rearrangement by deletion). We report here that Ssm1b expression and concomitant HRD methylation are also present in the male and female germ cells of adult mice. Ssm1b is expressed in both diploid (2N) and haploid (1N) oocytes, as well as in 1N spermatids and spermatozoa, but not in 2N spermatogonia. Interestingly, Ssm1b mRNA is not detected in any other adult mouse organ examined, although Ssm1-family mRNAs are highly expressed in the heart. Reflecting strain specificity, Ssm1b expression and HRD methylation are not observed in early-stage C3H/HeJ mouse embryos; however, an Ssm1b-like gene that closely resembles an Ssm1b-like gene previously found in wild-derived mice is expressed in cultured embryonic stem cells derived from C3H/HeJ embryos, suggesting that culture conditions affect its expression. Collectively, this work demonstrates that HRD methylation by Ssm1b is more temporally restricted during spermatogenesis compared to oogenesis, and is altered when embryonic stem cells are cultured from C3H/HeJ inner cell mass cells.
    Language English
    Publishing date 2017-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 20321-x
    ISSN 1098-2795 ; 1040-452X
    ISSN (online) 1098-2795
    ISSN 1040-452X
    DOI 10.1002/mrd.22826
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  10. Article: Transgenic mice with immunoglobulin genes.

    Storb, U

    Annual review of immunology

    1987  Volume 5, Page(s) 151–174

    MeSH term(s) Animals ; B-Lymphocytes/immunology ; B-Lymphocytes/metabolism ; Cell Differentiation ; Chimera ; Genetic Engineering ; Immunoglobulin G/genetics ; Immunoglobulin kappa-Chains/genetics ; Mice ; Mice, Inbred Strains/genetics ; Transcription, Genetic
    Chemical Substances Immunoglobulin G ; Immunoglobulin kappa-Chains
    Language English
    Publishing date 1987
    Publishing country United States
    Document type Journal Article ; Research Support, U.S. Gov't, P.H.S. ; Review
    ZDB-ID 604953-9
    ISSN 1545-3278 ; 0732-0582
    ISSN (online) 1545-3278
    ISSN 0732-0582
    DOI 10.1146/annurev.iy.05.040187.001055
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