@article {783,
	title = {Disease-associated CTNNBL1 mutation impairs somatic hypermutation by decreasing nuclear AID.},
	journal = {J Clin Invest},
	volume = {130},
	year = {2020},
	month = {2020 08 03},
	pages = {4411-4422},
	abstract = {<p>Patients with common variable immunodeficiency associated with autoimmune cytopenia (CVID+AIC) generate few isotype-switched B cells with severely decreased frequencies of somatic hypermutations (SHMs), but their underlying molecular defects remain poorly characterized. We identified a CVID+AIC patient who displays a rare homozygous missense M466V mutation in β-catenin-like protein 1 (CTNNBL1). Because CTNNBL1 binds activation-induced cytidine deaminase (AID) that catalyzes SHM, we tested AID interactions with the CTNNBL1 M466V variant. We found that the M466V mutation interfered with the association of CTNNBL1 with AID, resulting in decreased AID in the nuclei of patient EBV-transformed B cell lines and of CTNNBL1 466V/V Ramos B cells engineered to express only CTNNBL1 M466V using CRISPR/Cas9 technology. As a consequence, the scarce IgG+ memory B cells from the CTNNBL1 466V/V patient showed a low SHM frequency that averaged 6.7 mutations compared with about 18 mutations per clone in healthy-donor counterparts. In addition, CTNNBL1 466V/V Ramos B cells displayed a decreased incidence of SHM that was reduced by half compared with parental WT Ramos B cells, demonstrating that the CTNNBL1 M466V mutation is responsible for defective SHM induction. We conclude that CTNNBL1 plays an important role in regulating AID-dependent antibody diversification in humans.</p>},
	keywords = {Amino Acid Substitution, Apoptosis Regulatory Proteins, B-Lymphocytes, Cell Line, Child, Preschool, Common Variable Immunodeficiency, Cytidine Deaminase, Female, Homozygote, Humans, Immunologic Memory, Mutation, Missense, Nuclear Proteins, Somatic Hypermutation, Immunoglobulin},
	issn = {1558-8238},
	doi = {10.1172/JCI131297},
	author = {Kuhny, Marcel and Forbes, Lisa R and {\c C}akan, Elif and Vega-Loza, Andrea and Kostiuk, Valentyna and Dinesh, Ravi K and Glauzy, Salom{\'e} and Stray-Pedersen, Asbjorg and Pezzi, Ashley E and Hanson, I Celine and Vargas-Hernandez, Alexander and Xu, Mina LuQuing and Coban-Akdemir, Zeynep H and Jhangiani, Shalini N and Muzny, Donna M and Gibbs, Richard A and Lupski, James R and Chinn, Ivan K and Schatz, David G and Orange, Jordan S and Meffre, Eric}
}
@article {937,
	title = {Human NK cell deficiency as a result of biallelic mutations in MCM10.},
	journal = {J Clin Invest},
	volume = {130},
	year = {2020},
	month = {2020 10 01},
	pages = {5272-5286},
	abstract = {<p>Human natural killer cell deficiency (NKD) arises from inborn errors of immunity that lead to impaired NK cell development, function, or both. Through the understanding of the biological perturbations in individuals with NKD, requirements for the generation of terminally mature functional innate effector cells can be elucidated. Here, we report a cause of NKD resulting from compound heterozygous mutations in minichromosomal maintenance complex member 10 (MCM10) that impaired NK cell maturation in a child with fatal susceptibility to CMV. MCM10 has not been previously associated with monogenic disease and plays a critical role in the activation and function of the eukaryotic DNA replisome. Through evaluation of patient primary fibroblasts, modeling patient mutations in fibroblast cell lines, and MCM10 knockdown in human NK cell lines, we have shown that loss of MCM10 function leads to impaired cell cycle progression and induction of DNA damage-response pathways. By modeling MCM10 deficiency in primary NK cell precursors, including patient-derived induced pluripotent stem cells, we further demonstrated that MCM10 is required for NK cell terminal maturation and acquisition of immunological system function. Together, these data define MCM10 as an NKD gene and provide biological insight into the requirement for the DNA replisome in human NK cell maturation and function.</p>},
	keywords = {Alleles, Cell Cycle Checkpoints, Cell Differentiation, Cell Line, Codon, Nonsense, DNA Damage, Fatal Outcome, Female, Gene Knockdown Techniques, Heterozygote, Humans, Induced Pluripotent Stem Cells, Infant, Killer Cells, Natural, Male, Minichromosome Maintenance Proteins, Models, Immunological, Mutation, Mutation, Missense, Pedigree, Primary Immunodeficiency Diseases},
	issn = {1558-8238},
	doi = {10.1172/JCI134966},
	author = {Mace, Emily M and Paust, Silke and Conte, Matilde I and Baxley, Ryan M and Schmit, Megan M and Patil, Sagar L and Guilz, Nicole C and Mukherjee, Malini and Pezzi, Ashley E and Chmielowiec, Jolanta and Tatineni, Swetha and Chinn, Ivan K and Akdemir, Zeynep Coban and Jhangiani, Shalini N and Muzny, Donna M and Stray-Pedersen, Asbj{\o}rg and Bradley, Rachel E and Moody, Mo and Connor, Philip P and Heaps, Adrian G and Steward, Colin and Banerjee, Pinaki P and Gibbs, Richard A and Borowiak, Malgorzata and Lupski, James R and Jolles, Stephen and Bielinsky, Anja K and Orange, Jordan S}
}
