A Hyper-IgM Syndrome Mutation in Activation-Induced Cytidine Deaminase Disrupts G-Quadruplex Binding and Genome-wide Chromatin Localization

• Published in: Immunity (Cambridge, Mass.) Vol. 53; no. 5; pp. 952 - 970.e11
• Main Authors: Yewdell, William T., Kim, Youngjun, Chowdhury, Priyanka, Lau, Colleen M., Smolkin, Ryan M., Belcheva, Kalina T., Fernandez, Keith C., Cols, Montserrat, Yen, Wei-Feng, Vaidyanathan, Bharat, Angeletti, Davide, McDermott, Adrian B., Yewdell, Jonathan W., Sun, Joseph C., Chaudhuri, Jayanta
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 17.11.2020; Elsevier Limited
• Subjects: Activation-induced cytidine deaminase; AID; Animals; Antibodies; B-cell lymphoma; B-Lymphocytes - immunology; B-Lymphocytes - metabolism; Binding; Chromatin; Chromatin - genetics; Chromatin - metabolism; class switch recombination; Class switching; Computational Biology - methods; CSR; Cytidine deaminase; Cytidine Deaminase - genetics; Cytidine Deaminase - metabolism; Deoxyribonucleic acid; diffuse large B cell lymphoma; Disease Models, Animal; Disease Susceptibility; DLBCL; DNA; Enzyme Activation; Fluorescent Antibody Technique; G-quadruplex; G-Quadruplexes; Gene expression; Gene Expression Profiling; Genes; Genome-Wide Association Study; Genomes; Germinal Center - immunology; Germinal Center - metabolism; germinal center B cells; HIGM; HLA Antigens - genetics; HLA Antigens - immunology; Humans; Hyper-IgM Immunodeficiency Syndrome - diagnosis; Hyper-IgM Immunodeficiency Syndrome - etiology; Hyper-IgM Immunodeficiency Syndrome - metabolism; hyper-IgM syndrome; Hyperplasia; Immune system; Immunoglobulin Class Switching - genetics; Immunoglobulin Class Switching - immunology; Immunoglobulin M; Immunophenotyping; Job's syndrome; Localization; Loci; Lymphocyte Activation - genetics; Lymphocytes B; Lymphoma; Lymphoma, Large B-Cell, Diffuse - etiology; Lymphoma, Large B-Cell, Diffuse - metabolism; Lymphoma, Large B-Cell, Diffuse - pathology; MHC class II; MHCII; Mice; Mice, Transgenic; Mutation; Nucleic acids; Pathogens; Pathology; Recombination; SHM; Somatic hypermutation; Spleen; DLBCL; CSR; diffuse large B cell lymphoma; activation-induced cytidine deaminase; HIGM; G-quadruplex; MHC class II; class switch recombination; G4; hyper-IgM syndrome; somatic hypermutation; MHCII; SHM; AID; germinal center B cells

Precise targeting of activation-induced cytidine deaminase (AID) to immunoglobulin (Ig) loci promotes antibody class switch recombination (CSR) and somatic hypermutation (SHM), whereas AID targeting of non-Ig loci can generate oncogenic DNA lesions. Here, we examined the contribution of G-quadruplex...