نتایج جستجو برای: somatic hypermutation
تعداد نتایج: 43405 فیلتر نتایج به سال:
Somatic hypermutation of the immunoglobulin variable genes during germinal reactions might permit the expansion of B-cell clones with unwanted (e.g. autoreactive) specificity. Here, Ernst Lindhout and colleagues propose three antigen-specific checkpoints that ensure the appropriate antigen specificity of activated B cells is maintained by regulating the activation, selection and further differe...
The contribution of proliferation to B lymphocyte homeostasis and antigen responses is largely unknown. We quantified the replication history of mouse and human B lymphocyte subsets by calculating the ratio between genomic coding joints and signal joints on kappa-deleting recombination excision circles (KREC) of the IGK-deleting rearrangement. This approach was validated with in vitro prolifera...
Somatic hypermutation and class switch recombination (CSR) contribute to the somatic diversification of antibodies. It has been shown that MutS homologue (Msh)6 (in conjunction with Msh2) but not Msh3 is involved in generating A/T base substitutions in somatic hypermutation. However, their roles in CSR have not yet been reported. Here we show that Msh6(-)(/)(-) mice have a decrease in CSR, wher...
Graves' disease results from thyroid-stimulating Abs (TSAbs) activating the thyrotropin receptor (TSHR). How TSAbs arise from early precursor B cells has not been established. Genetic and environmental factors may contribute to pathogenesis, including the bacterium Yersinia enterocolitica. We developed two pathogenic monoclonal TSAbs from a single experimental mouse undergoing Graves' disease, ...
In systemic lupus erythematosus (SLE) it has been hypothesized that self-reactive B cells arise from virgin B cells that express low-affinity, nonpathogenic germline V genes that are cross-reactive for self and microbial antigens, which convert to high-affinity autoantibodies via somatic hypermutation. The aim of the present study was to determine whether the VH family repertoire and pattern of...
Myeloma VL and VH gene sequences reveal a complementary imprint of antigen selection in tumor cells.
In multiple myeloma, sequence studies of VH genes used to encode clonal Ig in neoplastic plasma cells have shown a common pattern of extensive somatic hypermutation. A further consistent feature of these VH sequences is a complete lack of intraclonal variation. These findings indicate that the malignant cell arises at a mature, postfollicular stage of B-cell development. However, only a minorit...
To gain insight into the genomic basis of diffuse large B-cell lymphoma (DLBCL), we performed massively parallel whole-exome sequencing of 55 primary tumor samples from patients with DLBCL and matched normal tissue. We identified recurrent mutations in genes that are well known to be functionally relevant in DLBCL, including MYD88, CARD11, EZH2, and CREBBP. We also identified somatic mutations ...
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