Abstract
We found previously that the Ig in FL is unusual, because the variable region genes carry sequence motifs for N-glycan addition. These are introduced by somatic mutation and are tumor specific. Unexpectedly, added glycans terminate at high mannose, suggesting a potentially important interaction of F...
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PMID: 20937880
PDF is available here.
Abstract
Some IgM cattle antibodies are amongst the largest known to exist in jawed vertebrates where CDR3H size may extend up to 61 amino acids. To understand the origin of such an exceptionally long CDR3H, bovine D(H) gene locus was completely characterized from Holstein cattle that revealed the presence o...
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PMID: 20435350
PDF is available here.
Abstract
We show that a POLH(-/-)/POLN(-/-)/POLQ(-/-) triple mutant displays no Ig gene conversion and reduced Ig hypermutation. Together, these data define a role for Polnu and Pol in recombination and suggest that the DNA synthesis associated with Ig gene conversion is accounted for by three specialized DN...
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PMID: 20584917
PDF is available here.
Abstract
We show that a POLH(-/-)/POLN(-/-)/POLQ(-/-) triple mutant displays no Ig gene conversion and reduced Ig hypermutation. Together, these data define a role for Polnu and Pol in recombination and suggest that the DNA synthesis associated with Ig gene conversion is accounted for by three specialized DN...
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PMID: 20584917
PDF is available here.
Abstract
We previously generated an engineered DT40 line named DT40-SW, whose AID expression can be reversibly switched on or off, and developed an in vitro Ab generation system using DT40-SW cells. To efficiently create an Ab library with sufficient diversity, higher hypermutation frequency is advantageous....
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PMID: 20416279
PDF is available here.
Abstract
We investigated AID-mRNA isoform expression in a series of 195 CLL patients and explored associations with IG gene mutational status and surface immunoglobulin (sIg) isotype expression. Full-length AID transcripts and two splice variants were detected in 110/91/95 cases, respectively. Co-expression...
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PMID: 20117026
PDF is available here.
Abstract
We characterized IgD(+) tonsillar GC cells. GC dominated by IgD(+) B cells were present in 10 of 67 tonsils analyzed. Three GC were additionally positive for CD70. Detailed analysis of one such GC by microdissection and single-cell DNA PCR revealed IgD(+) GC B cells undergoing somatic hypermutation...
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PMID: 20139173
PDF is available here.
Abstract
Japanese scientists were involved in pioneering work on therapeutic antisera and have made huge contributions to the characterization of the antibody molecules that are responsible for this and many other biological activities, as well as working back to understand the B cells that p...
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PMID: 20139175
PDF is available here.
Abstract
We favour the hypothesis that post-apoptotic debris accumulates in germinal centres, activates complement, and serves as a survival signal for B-cells that had stochastically become autoreactive in the process of somatic hypermutation (etiology). In the presence of autoantibodies against apoptotic c...
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PMID: 20107814
PDF is available here.
Abstract
The investigation of an inherited primary immunodeficiency, the immunoglobulin class switch recombination deficiency, has allowed the delineation of complex molecular events that underlie antibody maturation in humans. The Activation-induced cytidine deaminase (AID)-deficiency, characterized by a de...
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PMID: 20687504
PDF is available here.
Abstract
We assessed p53-IHC in 222 bone marrow (BM) specimens from patients with CLL enrolled in a phase II trial with fludarabine, cyclophosphamide, and rituximab (FCR). ZAP70 expression and IgVH MS were assessed in 208 and 108 patients, respectively. One hundred sixty-eight patients had concurrent classic...
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PMID: 19863337
PDF is available here.
Abstract
Ability to make an optimal immune response to vaccines and infectious agents declines with age in humans and animal models. Recent advances have shown intrinsic B cell defects in aged mice and humans, including decreases in Ig class switch recombination (CSR), activation-induced cytidine deaminase (...
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PMID: 19608393
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
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PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We have developed a quantitative method to study directional transcription. Our method controls for differences in efficiency and specificity of reverse transcription that are known to be able to generate false positive data. This method does not detect antisense transcripts in exonic or intronic re...
|
PMID: 19403175
PDF is available here.
Abstract
We previously suggested that another polymerase with a different mutation signature, Pol {kappa}, is used as backup for Ig gene hypermutation in both humans and mice in cases of complete Pol {eta} deficiency, a proposition supported in this study by the analysis of Pol {eta} x Pol {kappa} double-def...
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PMID: 19414788
PDF is available here.
Abstract
We analysed the mutation spectrum of somatically mutated immunoglobulin genes in B cells from PCNAK164R knock-in mice. A 10-fold reduction in A/T mutations is associated with a compensatory increase in G/C mutations-a phenotype similar to Poleta and mismatch repair-deficient B cells. Mismatch recogn...
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PMID: 19008189
PDF is available here.
Abstract
We specifically consider the control of translesion synthesis in the context of the timing of lesion bypass relative to replication fork progression and arrest at sites of DNA damage. We then examine how recent observations concerning the control of translesion synthesis might help refine our view o...
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PMID: 19008194
PDF is available here.
Abstract
We first studied the role of mismatch repair proteins, MSH2, MSH3, MSH6, PMS2 and MLH1, since they would recognize mismatches. The MSH2-MSH6 heterodimer is involved in hypermutation by binding to U:G and other mismatches generated during repair synthesis, but the other proteins are not necessary. Se...
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PMID: 19008198
PDF is available here.
Abstract
We discuss our interpretation of the significance of AID regulation via phosphorylation and also discuss how this form of AID regulation may have evolved in higher organisms....
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PMID: 19010772
PDF is available here.
Abstract
We review here how the studies in DT40 contributed to understanding how AID initiates Ig gene diversification and how AID-induced uracils are subsequently processed by uracil DNA glycosylase, proliferating cell nuclear antigens and error-prone polymerases. We also discuss the on-going research on th...
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PMID: 19008193
PDF is available here.
Abstract
This review focuses on the contribution of translesion DNA polymerases to immunoglobulin gene hypermutation, in particular on the roles of DNA polymerase eta (Poleta) in the generation of mutations at A/T bases from the initial cytosine-targeted activation-induced cytidine deaminase (AID)-mediated d...
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PMID: 19010770
PDF is available here.
Abstract
We show here that CD4(+) follicular helper T cells constituted essentially all of the cytokine-secreting T cells in lymph nodes and were functionally distinct from T cells secreting the same cytokine in peripheral tissues. Follicular helper T cells with different cytokine profiles could be isolated...
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PMID: 19252490
PDF is available here.
Riccardo Bomben,
Michele Dal Bo,
Daniela Capello,
Francesco Forconi,
Rossana Maffei,
Luca Laurenti,
Davide Rossi,
Maria Ilaria Del Principe,
Antonella Zucchetto,
Francesco Bertoni,
Francesca Maria Rossi,
Pietro Bulian,
Ilaria Cattarossi,
Fiorella Ilariucci,
Elisa Sozzi,
Valeria Spina,
Emanuele Zucca,
Massimo Degan,
Francesco Lauria,
Giovanni Del Poeta,
Dimitar G Efremov,
Roberto Marasca,
Gianluca Gaidano and
Valter Gattei
Abstract
We analysed 1426 IG rearrangements (from 1398 CLL cases) by a clustering driven by HCDR3 similarities. Molecular findings were correlated to time-to-treatment (TTT) and presence of known prognosticators. Sixty-nine clusters (319 IG-rearrangements, 22.4%) with stereotyped BCR were identified. Among 3...
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PMID: 19036101
PDF is available here.
Abstract
We showed that AID is implicated in the pathogenesis of human cancers including hepatitis C virus (HCV)-induced human hepatocellular carcinoma (HCC). In this study, we established a new AID transgenic mouse model (TNAP-AID) in which AID is expressed in cells producing tissue-nonspecific alkaline pho...
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PMID: 18997814
PDF is available here.
Abstract
We studied the mutational profile of PAX5, RhoH/TTF, cMYC, and PIM1 in 11 PCMZLs. A total of 17 sequence variants were found in 8 of 11 lymphomas cases (72.7%), and they displayed the molecular features typical for the ASHM. Further, two mutations, one mutation in PIM1 and one in cMYC, led to amino-...
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PMID: 18704108
PDF is available here.
Abstract
We show that normal GC human B cells and blood memory B cells similarly express AID splice variants and show for the first time that AID splicing variants are singly expressed in individual normal B cells as well as malignant B cells from chronic lymphocytic leukemia patients. We further demonstrate...
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PMID: 18684869
PDF is available here.
Abstract
We identified V(H)-->V(H)(D)J(H) compound rearrangements from fetal liver, fetal bone marrow, and naive peripheral blood, all of which involved invading and recipient V(H)4 genes that contain a cryptic heptamer, a 13-bp spacer, and nonamer in the 5' portion of framework region 3. Surprisingly, all p...
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PMID: 19017972
PDF is available here.