Villa A, Notarangelo LD. RAG gene defects at the verge of immunodeficiency and immune dysregulation. Immunol Rev. 2019;287(1):73–90.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Farmer JR, Foldvari Z, Ujhazi B, De Ravin SS, Chen K, Bleesing JJH, et al. Outcomes and treatment strategies for autoimmunity and hyperinflammation in patients with RAG deficiency. J Allergy Clin Immunol Pract. 2019;7(6):1970-85.e4.

Article  PubMed  PubMed Central  Google Scholar 

Henrickson SE, Walter JE, Quinn C, Kanakry JA, Bardakjian T, Dimitrova D, et al. Adult-onset myopathy in a patient with hypomorphic RAG2 mutations and combined immune deficiency. J Clin Immunol. 2018;38(6):642–5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

De Ravin SS, Cowen EW, Zarember KA, Whiting-Theobald NL, Kuhns DB, Sandler NG, et al. Hypomorphic Rag mutations can cause destructive midline granulomatous disease. Blood. 2010;116(8):1263–71.

Article  PubMed  PubMed Central  Google Scholar 

Buchbinder D, Baker R, Lee YN, Ravell J, Zhang Y, McElwee J, et al. Identification of patients with rag mutations previously diagnosed with common variable immunodeficiency disorders. J Clin Immunol. 2015;119–24.

Notarangelo LD, Kim MS, Walter JE, Lee YN. Human RAG mutations: biochemistry and clinical implications. Nat Rev Immunol. 2016;16(4):234–46.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Tirosh I, Yamazaki Y, Frugoni F, Ververs FA, Allenspach EJ, Zhang Y, et al. Recombination activity of human recombination-activating gene 2 (RAG2) mutations and correlation with clinical phenotype. J Allergy Clin Immunol. 2019;143(2):726–35.

Article  CAS  PubMed  Google Scholar 

IJspeert H, Driessen GJ, Moorhouse MJ, Hartwig NG, Wolska-Kusnierz B, Kalwak K, et al. Similar recombination-activating gene (RAG) mutations result in similar immunobiological effects but in different clinical phenotypes. J Allergy Clin Immunol. 2014;133(4):1124–33.

Schuetz C, Pannicke U, Jacobsen EM, Burggraf S, Albert MH, Hönig M, et al. Lesson from hypomorphic recombination-activating gene (RAG) mutations: Why asymptomatic siblings should also be tested. J Allergy Clin Immunol. 2014;133(4):1211–5.

Article  CAS  PubMed  Google Scholar 

Corneo B, Moshous D, Güngör T, Wulffraat N, Philippet P, Le Deist FL, et al. Identical mutations in RAG1 or RAG2 genes leading to defective V(D)J recombinase activity can cause either T-B-severe combined immune deficiency or Omenn syndrome. Blood. 2001;97(9):2772–6.

Article  CAS  PubMed  Google Scholar 

Pasic S, Djuricic S, Ristic G, Slavkovic B. Recombinase-activating gene 1 immunodeficiency: different immunological phenotypes in three siblings. Acta Paediatr. 2009;98(6):1062–4.

Article  CAS  PubMed  Google Scholar 

Chou J, Hanna-Wakim R, Tirosh I, Kane J, Fraulino D, Lee YN, et al. A novel homozygous mutation in recombination activating gene 2 in 2 relatives with different clinical phenotypes: Omenn syndrome and hyper-IgM syndrome. J Allergy Clin Immunol. 2012;130(6):1414–6.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Chen K, Wu W, Mathew D, Zhang Y, Browne SK, Rosen LB, et al. Autoimmunity due to RAG deficiency and estimated disease incidence in RAG1/2 mutations. J Allergy Clin Immunol. 2014;133(3):880-2.e10.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Martinez-Martinez L, Vazquez-Ortiz M, Gonzalez-Santesteban C, Martin-Nalda A, Vicente A, Plaza AM, et al. From severe combined immunodeficiency to omenn syndrome after hematopoietic stem cell transplantation in a RAG1 deficient family. Pediatr Allergy Immunol. 2012;23(7):660–6.

Article  PubMed  Google Scholar 

Sharapova SO, Guryanova IE, Pashchenko OE, Kondratenko IV, Kostyuchenko LV, Rodina YA, et al. Molecular characteristics, clinical and immunologic manifestations of 11 children with omenn syndrome in east slavs (Russia, Belarus, Ukraine). J Clin Immunol. 2016;36(1):46–55.

Article  CAS  PubMed  Google Scholar 

Ehl S, Schwarz K, Enders A, Duffner U, Pannicke U, Kühr J, et al. A variant of SCID with specific immune responses and predominance of gamma delta T cells. J Clin Invest. 2005;115(11):3140–8.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Henderson LA, Frugoni F, Hopkins G, de Boer H, Pai SY, Lee YN, et al. Expanding the spectrum of recombination-activating gene 1 deficiency: a family with early-onset autoimmunity. J Allergy Clin Immunol. 2013;132(4):969-71.e1-2.

Article  CAS  PubMed  Google Scholar 

Lawless D, Geier CB, Farmer JR, Lango Allen H, Thwaites D, Atschekzei F, et al. Prevalence and clinical challenges among adults with primary immunodeficiency and recombination-activating gene deficiency. J Allergy Clin Immunol. 2018;141(6):2303–6.

Article  PubMed  PubMed Central  Google Scholar 

Delmonte OM, Villa A, Notarangelo LD. Immune dysregulation in patients with RAG deficiency and other forms of combined immune deficiency. Blood. 2020;135(9):610–9.

Article  PubMed  PubMed Central  Google Scholar 

Csomos K, Ujhazi B, Blazso P, Herrera JL, Tipton CM, Kawai T, et al. Partial RAG deficiency in humans induces dysregulated peripheral lymphocyte development and humoral tolerance defect with accumulation of T-bet+ B cells. Nat Immunol. 2022;23(8):1256–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

de Villartay JP, Lim A, Al-Mousa H, Dupont S, Déchanet-Merville J, Coumau-Gatbois E, et al. A novel immunodeficiency associated with hypomorphic RAG1 mutations and CMV infection. J Clin Invest. 2005;115(11):3291–9.

Article  PubMed  PubMed Central  Google Scholar 

Rowe JH, Stadinski BD, Henderson LA, Ott de Bruin L, Delmonte O, Lee YN, et al. Abnormalities of T-cell receptor repertoire in CD4+ regulatory and conventional T cells in patients with RAG mutations: Implications for autoimmunity. J Allergy Clin Immunol. 2017;140(6):1739–43.e7.

Keller B, Warnatz K.T-bethighCD21low B cells: the need to unify our understanding of a distinct B cell population in health and disease. Curr Opin Immunol. 2023;82:102300.

Zhao Y, Uduman M, Siu JHY, Tull TJ, Sanderson JD, Wu YCB, et al. Spatiotemporal segregation of human marginal zone and memory B cell populations in lymphoid tissue. Nat Commun. 2018;9(1):3857.

Article  PubMed  PubMed Central  Google Scholar 

Palm AE, Kleinau S. Marginal zone B cells: From housekeeping function to autoimmunity? J Autoimmun. 2021;119:102627.

Article  CAS  PubMed  Google Scholar 

Riccetto AGL, Buzolin M, Fernandes JF, Traina F, Barjas-de-Castro MLR, Silva MTN, et al. Compound heterozygous RAG2 mutations mimicking hyper IgM syndrome. J Clin Immunol. 2014;34(1):7–9.

Article  CAS  PubMed  Google Scholar 

Renner ED, Hartl D, Rylaarsdam S, Young ML, Monaco-Shawver L, Kleiner G, et al. Comèl-Netherton syndrome defined as primary immunodeficiency. J Allergy Clin Immunol. 2009;124(3):536–43.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Allenspach EJ, Soveg F, Finn LS, So L, Gorman JA, Rosen ABI, et al. Germline SAMD9L truncation variants trigger global translational repression. J Exp Med. 2021;218(5):e20201195.

Lee YN, Frugoni F, Dobbs K, Tirosh I, Du L, Ververs FA, et al. Characterization of T and B cell repertoire diversity in patients with RAG deficiency. Sci Immunol. 2016;1(6):eaah6109.

Cheng RYH, Hung KL, Zhang T, Stoffers CM, Ott AR, Suchland ER, et al. Ex vivo engineered human plasma cells exhibit robust protein secretion and long-term engraftment in vivo. Nat Commun. 2022;13(1):6110.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Robins HS, Campregher PV, Srivastava SK, Wacher A, Turtle CJ, Kahsai O, et al. Comprehensive assessment of T-cell receptor β-chain diversity in αβ T cells. Blood. 2009;114(19):4099–107.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Carlson CS, Emerson RO, Sherwood AM, Desmarais C, Chung MW, Parsons JM, et al. Using synthetic templates to design an unbiased multiplex PCR assay. Nat Commun. 2013;4:2680.

Article  PubMed  Google Scholar 

Tipton CM, Fucile CF, Darce J, Chida A, Ichikawa T, Gregoretti I, et al. Diversity, cellular origin and autoreactivity of antibody-secreting cell population expansions in acute systemic lupus erythematosus. Nat Immunol. 2015;16(7):755–65.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Li QZ, Zhou J, Wandstrat AE, Carr-Johnson F, Branch V, Karp DR, Mohan C, Wakeland EK, Olsen NJ. Protein array autoantibody profiles for insights into systemic lupus erythematosus and inco