PMID- 30814336 OWN - NLM STAT- MEDLINE DCOM- 20200221 LR - 20220309 IS - 1946-6242 (Electronic) IS - 1946-6234 (Print) IS - 1946-6234 (Linking) VI - 11 IP - 481 DP - 2019 Feb 27 TI - Shaping of infant B cell receptor repertoires by environmental factors and infectious disease. LID - 10.1126/scitranslmed.aat2004 [doi] LID - eaat2004 AB - Antigenic exposures at epithelial sites in infancy and early childhood are thought to influence the maturation of humoral immunity and modulate the risk of developing immunoglobulin E (IgE)-mediated allergic disease. How different kinds of environmental exposures influence B cell isotype switching to IgE, IgG, or IgA, and the somatic mutation maturation of these antibody pools, is not fully understood. We sequenced antibody repertoires in longitudinal blood samples in a birth cohort from infancy through the first 3 years of life and found that, whereas IgG and IgA show linear increases in mutational maturation with age, IgM and IgD mutations are more closely tied to pathogen exposure. IgE mutation frequencies are primarily increased in children with impaired skin barrier conditions such as eczema, suggesting that IgE affinity maturation could provide a mechanistic link between epithelial barrier failure and allergy development. CI - Copyright (c) 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. FAU - Nielsen, Sandra C A AU - Nielsen SCA AUID- ORCID: 0000-0003-4746-8287 AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. FAU - Roskin, Krishna M AU - Roskin KM AUID- ORCID: 0000-0002-5864-5093 AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. AD - Department of Pediatrics, University of Cincinnati, Cincinnati, OH 45229, USA. AD - Division of Biomedical Informatics, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA. FAU - Jackson, Katherine J L AU - Jackson KJL AUID- ORCID: 0000-0002-9952-7069 AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. AD - Immunology Division, Garvan Institute of Medical Research, Darlinghurst, NSW 2010, Australia. FAU - Joshi, Shilpa A AU - Joshi SA AUID- ORCID: 0000-0002-8014-1529 AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. FAU - Nejad, Parastu AU - Nejad P AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. FAU - Lee, Ji-Yeun AU - Lee JY AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. FAU - Wagar, Lisa E AU - Wagar LE AUID- ORCID: 0000-0001-5980-3586 AD - Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. FAU - Pham, Tho D AU - Pham TD AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. AD - Stanford Blood Center, Palo Alto, CA 94304, USA. FAU - Hoh, Ramona A AU - Hoh RA AUID- ORCID: 0000-0002-5116-1942 AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. FAU - Nguyen, Khoa D AU - Nguyen KD AUID- ORCID: 0000-0003-3149-3621 AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. FAU - Tsunemoto, Hannah Y AU - Tsunemoto HY AUID- ORCID: 0000-0002-1546-097X AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. FAU - Patel, Sonal B AU - Patel SB AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. FAU - Tibshirani, Robert AU - Tibshirani R AUID- ORCID: 0000-0003-0553-5090 AD - Department of Biomedical Data Sciences, Stanford University, Stanford, CA 94305, USA. AD - Department of Statistics, Stanford University, Stanford, CA 94305, USA. FAU - Ley, Catherine AU - Ley C AUID- ORCID: 0000-0002-8424-7873 AD - Department of Medicine, Stanford University, Stanford, CA 94305, USA. FAU - Davis, Mark M AU - Davis MM AUID- ORCID: 0000-0001-6868-657X AD - Department of Microbiology and Immunology, Stanford University, Stanford, CA 94305, USA. AD - Howard Hughes Medical Institute, Stanford University, Stanford, CA 94305, USA. FAU - Parsonnet, Julie AU - Parsonnet J AUID- ORCID: 0000-0001-7342-5366 AD - Department of Medicine, Stanford University, Stanford, CA 94305, USA. sboyd1@stanford.edu parsonnt@stanford.edu. AD - Department of Health Research and Policy, Stanford University, Stanford, CA 94305, USA. FAU - Boyd, Scott D AU - Boyd SD AUID- ORCID: 0000-0003-0963-044X AD - Department of Pathology, Stanford University, Stanford, CA 94305, USA. sboyd1@stanford.edu parsonnt@stanford.edu. LA - eng GR - R01 HD063142/HD/NICHD NIH HHS/United States GR - U19 AI090019/AI/NIAID NIH HHS/United States GR - UL1 TR001085/TR/NCATS NIH HHS/United States GR - R01 AI130398/AI/NIAID NIH HHS/United States GR - U19 AI057229/AI/NIAID NIH HHS/United States GR - R01 AI125567/AI/NIAID NIH HHS/United States GR - UL1 RR025744/RR/NCRR NIH HHS/United States GR - R01 AI127877/AI/NIAID NIH HHS/United States PT - Journal Article PT - Observational Study PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PL - United States TA - Sci Transl Med JT - Science translational medicine JID - 101505086 RN - 0 (Antibodies) RN - 0 (Antigens) RN - 0 (Carbanilides) RN - 0 (Immunoglobulin Heavy Chains) RN - 0 (Immunoglobulin Variable Region) RN - 0 (Receptors, Antigen, B-Cell) RN - 0 (Vaccines) RN - 37341-29-0 (Immunoglobulin E) RN - BGG1Y1ED0Y (triclocarban) SB - IM MH - Adult MH - Aging MH - Antibodies/genetics MH - Antigens/immunology MH - B-Lymphocytes/immunology MH - Carbanilides MH - Child, Preschool MH - Clone Cells MH - Communicable Diseases/*immunology MH - Eczema/immunology MH - *Environment MH - Family Characteristics MH - Female MH - Humans MH - Hypersensitivity/immunology MH - Immunoglobulin Class Switching MH - Immunoglobulin E/metabolism MH - Immunoglobulin Heavy Chains/genetics MH - Immunoglobulin Variable Region/genetics MH - Infant MH - Male MH - Receptors, Antigen, B-Cell/*metabolism MH - Somatic Hypermutation, Immunoglobulin MH - Vaccines/immunology PMC - PMC6733608 MID - NIHMS1046762 COIS- Competing interests: The authors declare that they have no competing interests. S.D.B. has consulted as an expert witness for Regeneron and Sanofi on topics unrelated to the present study. EDAT- 2019/03/01 06:00 MHDA- 2020/02/23 06:00 PMCR- 2019/09/09 CRDT- 2019/03/01 06:00 PHST- 2018/02/02 00:00 [received] PHST- 2018/11/15 00:00 [revised] PHST- 2019/01/22 00:00 [accepted] PHST- 2019/03/01 06:00 [entrez] PHST- 2019/03/01 06:00 [pubmed] PHST- 2020/02/23 06:00 [medline] PHST- 2019/09/09 00:00 [pmc-release] AID - 11/481/eaat2004 [pii] AID - 10.1126/scitranslmed.aat2004 [doi] PST - ppublish SO - Sci Transl Med. 2019 Feb 27;11(481):eaat2004. doi: 10.1126/scitranslmed.aat2004.