A Public Database of Memory and Naive B-Cell Receptor Sequences

Abstract

The vast diversity of B-cell receptors (BCR) and secreted antibodies enables the recognition of, and response to, a wide range of epitopes, but this diversity has also limited our understanding of humoral immunity. We present a public database of more than 37 million unique BCR sequences from three healthy adult donors that is many fold deeper than any existing resource, together with a set of online tools designed to facilitate the visualization and analysis of the annotated data. We estimate the clonal diversity of the naive and memory B-cell repertoires of healthy individuals, and provide a set of examples that illustrate the utility of the database, including several views of the basic properties of immunoglobulin heavy chain sequences, such as rearrangement length, subunit usage, and somatic hypermutation positions and dynamics.

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References 63

1. 1.

   Davis MM, Calame K, Early PW, Livant DL, Joho R, Weissman IL, et al An immunoglobulin heavy-chain gene is formed by at least two recombinational events. Nature. 1980;283(5749):733–9. Epub 1980/02/21..

   Not in our library10.1038/283733a0

2. 2.

   Watson CT, Steinberg KM, Huddleston J, Warren RL, Malig M, Schein J, et al Complete haplotype sequence of the human immunoglobulin heavy-chain variable, diversity, and joining genes and characterization of allelic and copy-number variation. Am J Hum Genet. 2013;92(4):530–46. Epub 2013/04/02.

   Not in our library10.1016/j.ajhg.2013.03.004

3. 3.

   Murphy K, Travers P, Walport M. Janeway's Immunobiology. 7th ed. New York, NY: Garland Science; 2008.

   Not in our library

4. 4.

   Muramatsu M, Kinoshita K, Fagarasan S, Yamada S, Shinkai Y, Honjo T. Class switch recombination and hypermutation require activation-induced cytidine deaminase (AID), a potential RNA editing enzyme. Cell. 2000;102(5):553–63. Epub 2000/09/28..

   Not in our library10.1016/s0092-8674(00)00078-7

5. 5.

   Jacob J, Kelsoe G, Rajewsky K, Weiss U. Intraclonal generation of antibody mutants in germinal centres. Nature. 1991;354(6352):389–92. Epub 1991/12/05..

   Not in our library10.1038/354389a0

6. 6.

   Pham P, Bransteitter R, Petruska J, Goodman MF. Processive AID-catalysed cytosine deamination on single-stranded DNA simulates somatic hypermutation. Nature. 2003;424(6944):103–7. Epub 2003/06/24..

   Not in our library10.1038/nature01760

7. 7.

   Calis JJ, Rosenberg BR. Characterizing immune repertoires by high throughput sequencing: strategies and applications. Trends Immunol. 2014;35(12):581–90.

   Not in our library10.1016/j.it.2014.09.004

8. 8.
   The Past, Present, and Future of Immune Repertoire Biology – The Rise of Next-Generation Repertoire Analysis · 2013

   No notice
9. 9.

   Giudicelli V, Duroux P, Ginestoux C, Folch G, Jabado-Michaloud J, Chaume D, et al IMGT/LIGM-DB, the IMGT comprehensive database of immunoglobulin and T cell receptor nucleotide sequences. Nucleic Acids Res. 2006;34(Database issue):D781–4.

   Not in our library10.1093/nar/gkj088

10. 10.
    High-Resolution Description of Antibody Heavy-Chain Repertoires in Humans · 2011

    No notice
11. 11.

    Boyd SD, Gaeta BA, Jackson KJ, Fire AZ, Marshall EL, Merker JD, et al Individual variation in the germline Ig gene repertoire inferred from variable region gene rearrangements. J Immunol. 2010;184(12):6986–92. Epub 2010/05/25.

    Not in our library10.4049/jimmunol.1000445

12. 12.

    Boyd SD, Marshall EL, Merker JD, Maniar JM, Zhang LN, Sahaf B, et al Measurement and clinical monitoring of human lymphocyte clonality by massively parallel VDJ pyrosequencing. Sci Transl Med. 2009;1(12):12ra23 Epub 2010/02/18.

    Not in our library10.1126/scitranslmed.3000540

13. 13.

    Briney BS, Willis JR, McKinney BA, Crowe JE Jr. High-throughput antibody sequencing reveals genetic evidence of global regulation of the naive and memory repertoires that extends across individuals. Genes Immun. 2012;13(6):469–73. Epub 2012/05/25.

    Not in our library10.1038/gene.2012.20

14. 14.

    DeKosky BJ, Ippolito GC, Deschner RP, Lavinder JJ, Wine Y, Rawlings BM, et al High-throughput sequencing of the paired human immunoglobulin heavy and light chain repertoire. Nat Biotechnol. 2013;31(2):166–9.

    Not in our library10.1038/nbt.2492

15. 15.

    DeKosky BJ, Kojima T, Rodin A, Charab W, Ippolito GC, Ellington AD, et al In-depth determination and analysis of the human paired heavy- and light-chain antibody repertoire. Nat Med. 2015;21(1):86–91.

    Not in our library10.1038/nm.3743

16. 16.

    Galson JD, Truck J, Clutterbuck EA, Fowler A, Cerundolo V, Pollard AJ, et al B-cell repertoire dynamics after sequential hepatitis B vaccination and evidence for cross-reactive B-cell activation. Genome Med. 2016;8(1):68

    Not in our library10.1186/s13073-016-0322-z

17. 17.

    Jackson KJ, Liu Y, Roskin KM, Glanville J, Hoh RA, Seo K, et al Human responses to influenza vaccination show seroconversion signatures and convergent antibody rearrangements. Cell Host Microbe. 2014;16(1):105–14.

    Not in our library10.1016/j.chom.2014.05.013

18. 18.

    Larimore K, McCormick MW, Robins HS, Greenberg PD. Shaping of human germline IgH repertoires revealed by deep sequencing. J Immunol. 2012;189(6):3221–30.

    Not in our library10.4049/jimmunol.1201303

19. 19.

    Laserson U, Vigneault F, Gadala-Maria D, Yaari G, Uduman M, Vander Heiden JA, et al High-resolution antibody dynamics of vaccine-induced immune responses. Proc Natl Acad Sci USA. 2014;111(13):4928–33.

    Not in our library10.1073/pnas.1323862111

20. 20.

    Prabakaran P, Chen W, Singarayan MG, Stewart CC, Streaker E, Feng Y, et al Expressed antibody repertoires in human cord blood cells: 454 sequencing and IMGT/HighV-QUEST analysis of germline gene usage, junctional diversity, and somatic mutations. Immunogenetics. 2012;64(5):337–50.

    Not in our library10.1007/s00251-011-0595-8

21. 21.

    Vollmers C, Sit RV, Weinstein JA, Dekker CL, Quake SR. Genetic measurement of memory B-cell recall using antibody repertoire sequencing. Proc Natl Acad Sci USA. 2013;110(33):13463–8.

    Not in our library10.1073/pnas.1312146110

22. 22.

    Strauli NB, Hernandez RD. Statistical inference of a convergent antibody repertoire response to influenza vaccine. Genome Med. 2016;8(1):60

    Not in our library10.1186/s13073-016-0314-z

23. 23.

    Wu D, Emerson RO, Sherwood A, Loh ML, Angiolillo A, Howie B, et al Detection of minimal residual disease in B lymphoblastic leukemia by high-throughput sequencing of IGH. Clin Cancer Res. 2014;20(17):4540–8.

    Not in our library10.1158/1078-0432.ccr-13-3231

24. 24.

    Cortina-Ceballos B, Godoy-Lozano EE, Tellez-Sosa J, Ovilla-Munoz M, Samano-Sanchez H, Aguilar-Salgado A, et al Longitudinal analysis of the peripheral B cell repertoire reveals unique effects of immunization with a new influenza virus strain. Genome Med. 2015;7:124

    Not in our library10.1186/s13073-015-0239-y

25. 25.

    Robins H. Immunosequencing: applications of immune repertoire deep sequencing. Curr Opin Immunol. 2013;25(5):646–52. Epub 2013/10/22..

    Not in our library10.1016/j.coi.2013.09.017

26. 26.

    Elhanati Y, Murugan A, Callan CG Jr., Mora T, Walczak AM. Quantifying selection in immune receptor repertoires. Proc Natl Acad Sci USA. 2014;111(27):9875–80. Epub 2014/06/20.

    Not in our library10.1073/pnas.1409572111

27. 27.

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

    Not in our library10.1182/blood-2009-04-217604

28. 28.

    Robins HS, Srivastava SK, Campregher PV, Turtle CJ, Andriesen J, Riddell SR, et al Overlap and effective size of the human CD8+ T cell receptor repertoire. Sci Transl Med. 2010;2(47):47ra64

    Not in our library10.1126/scitranslmed.3001442

29. 29.

    Sherwood AM, Desmarais C, Livingston RJ, Andriesen J, Haussler M, Carlson CS, et al Deep sequencing of the human TCRgamma and TCRbeta repertoires suggests that TCRbeta rearranges after alphabeta and gammadelta T cell commitment. Sci Transl Med. 2011;3(90):90ra61 Epub 2011/07/08.

    Not in our library10.1126/scitranslmed.3002536

30. 30.

    Wu D, Sherwood A, Fromm JR, Winter SS, Dunsmore KP, Loh ML, et al High-throughput sequencing detects minimal residual disease in acute T lymphoblastic leukemia. Sci Transl Med. 2012;4(134):134ra63

    Not in our library10.1126/scitranslmed.3003656

31. 31.

    Doria-Rose NA, Schramm CA, Gorman J, Moore PL, Bhiman JN, DeKosky BJ, et al Developmental pathway for potent V1V2-directed HIV-neutralizing antibodies. Nature. 2014;509(7498):55–62. Epub 2014/03/05

    Not in our library10.1038/nature13036

32. 32.

    Muraro PA, Robins H, Malhotra S, Howell M, Phippard D, Desmarais C, et al T cell repertoire following autologous stem cell transplantation for multiple sclerosis. J Clin Invest. 2014;124(3):1168–72.

    Not in our library10.1172/jci71691

33. 33.

    Schneider-Hohendorf T, Mohan H, Bien CG, Breuer J, Becker A, Gorlich D, et al CD8(+) T-cell pathogenicity in Rasmussen encephalitis elucidated by large-scale T-cell receptor sequencing. Nat Commun. 2016;7:11153

    Not in our library10.1038/ncomms11153

34. 34.

    DeWitt WS, Emerson RO, Lindau P, Vignali M, Snyder TM, Desmarais C, et al Dynamics of the cytotoxic T cell response to a model of acute viral infection. J Virol. 2015.

    Not in our library10.1128/jvi.03474-14

35. 35.

    Morris H, DeWolf S, Robins H, Sprangers B, LoCascio SA, Shonts BA, et al Tracking donor-reactive T cells: Evidence for clonal deletion in tolerant kidney transplant patients. Sci Transl Med. 2015;7(272):272ra10

    Not in our library10.1126/scitranslmed.3010760

36. 36.

    Emerson RO, Mathew JM, Konieczna IM, Robins HS, Leventhal JR. Defining the alloreactive T cell repertoire using high-throughput sequencing of mixed lymphocyte reaction culture. PLoS One. 2014;9(11):e111943

    Not in our library10.1371/journal.pone.0111943

37. 37.

    Emerson RO, Sherwood AM, Rieder MJ, Guenthoer J, Williamson DW, Carlson CS, et al High-throughput sequencing of T-cell receptors reveals a homogeneous repertoire of tumour-infiltrating lymphocytes in ovarian cancer. J Pathol. 2013;231(4):433–40.

    Not in our library10.1002/path.4260

38. 38.

    Tumeh PC, Harview CL, Yearley JH, Shintaku IP, Taylor EJ, Robert L, et al PD-1 blockade induces responses by inhibiting adaptive immune resistance. Nature. 2014;515(7528):568–71.

    Not in our library10.1038/nature13954

39. 39.

    Hsu MS, Sedighim S, Wang T, Antonios JP, Everson RG, Tucker AM, et al TCR Sequencing Can Identify and Track Glioma-Infiltrating T Cells after DC Vaccination. Cancer Immunol Res. 2016;4(5):412–8.

    Not in our library10.1158/2326-6066.cir-15-0240

40. 40.

    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

    Not in our library10.1038/ncomms3680

Cited by papers we hold 5

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• OLGA: fast computation of generation probabilities of B- and T-cell receptor amino acid sequences and motifs · 2019
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• Computational Strategies for Dissecting the High-Dimensional Complexity of Adaptive Immune Repertoires · 2018
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• Likelihood-Based Inference of B Cell Clonal Families. · 2016
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• Consistency of VDJ Rearrangement and Substitution Parameters Enables Accurate B Cell Receptor Sequence Annotation · 2016
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