Defining Antigen-specific Plasmablast and Memory B Cell Subsets in Human Blood After Viral Infection or Vaccination

Overview

Journal Nat Immunol

Date 2016 Aug 16

PMID 27525369

Citations 234

Authors

Ali H Ellebedy

Katherine J L Jackson

Haydn T Kissick

Helder I Nakaya

Carl W Davis

Krishna M Roskin

Anita K McElroy

Christine M Oshansky

Rivka Elbein

Shine Thomas

George M Lyon

Christina F Spiropoulou

Aneesh K Mehta

Paul G Thomas

Scott D Boyd

Rafi Ahmed

Affiliations

Soon will be listed here.

Abstract

Antigen-specific B cells bifurcate into antibody-secreting cells (ASCs) and memory B cells (MBCs) after infection or vaccination. ASCs (plasmablasts) have been extensively studied in humans, but less is known about B cells that become activated but do not differentiate into plasmablasts. Here we have defined the phenotype and transcriptional program of a subset of antigen-specific B cells, which we have called 'activated B cells' (ABCs), that were distinct from ASCs and were committed to the MBC lineage. We detected ABCs in humans after infection with Ebola virus or influenza virus and also after vaccination. By simultaneously analyzing antigen-specific ASCs and ABCs in human blood after vaccination against influenza virus, we investigated the clonal overlap and extent of somatic hypermutation (SHM) in the ASC (effector) and ABC (memory) lineages. Longitudinal tracking of vaccination-induced hemagglutinin (HA)-specific clones revealed no overall increase in SHM over time, which suggested that repeated annual immunization might have limitations in enhancing the quality of influenza-virus-specific antibody.

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References

Amanna I, Carlson N, Slifka M . Duration of humoral immunity to common viral and vaccine antigens. N Engl J Med. 2007; 357(19):1903-15. DOI: 10.1056/NEJMoa066092. View

Li G, Chiu C, Wrammert J, McCausland M, Andrews S, Zheng N . Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc Natl Acad Sci U S A. 2012; 109(23):9047-52. PMC: 3384143. DOI: 10.1073/pnas.1118979109. View

Xu H, Chaudhri V, Wu Z, Biliouris K, Dienger-Stambaugh K, Rochman Y . Regulation of bifurcating B cell trajectories by mutual antagonism between transcription factors IRF4 and IRF8. Nat Immunol. 2015; 16(12):1274-81. DOI: 10.1038/ni.3287. View

Subramanian A, Tamayo P, Mootha V, Mukherjee S, Ebert B, Gillette M . Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc Natl Acad Sci U S A. 2005; 102(43):15545-50. PMC: 1239896. DOI: 10.1073/pnas.0506580102. View

Nutt S, Kee B . The transcriptional regulation of B cell lineage commitment. Immunity. 2007; 26(6):715-25. DOI: 10.1016/j.immuni.2007.05.010. View

Saito R, Smoot M, Ono K, Ruscheinski J, Wang P, Lotia S . A travel guide to Cytoscape plugins. Nat Methods. 2012; 9(11):1069-76. PMC: 3649846. DOI: 10.1038/nmeth.2212. View

Nakaya H, Wrammert J, Lee E, Racioppi L, Marie-Kunze S, Nicholas Haining W . Systems biology of vaccination for seasonal influenza in humans. Nat Immunol. 2011; 12(8):786-95. PMC: 3140559. DOI: 10.1038/ni.2067. View

Corti D, Voss J, Gamblin S, Codoni G, Macagno A, Jarrossay D . A neutralizing antibody selected from plasma cells that binds to group 1 and group 2 influenza A hemagglutinins. Science. 2011; 333(6044):850-6. DOI: 10.1126/science.1205669. View

Purtha W, Tedder T, Johnson S, Bhattacharya D, Diamond M . Memory B cells, but not long-lived plasma cells, possess antigen specificities for viral escape mutants. J Exp Med. 2011; 208(13):2599-606. PMC: 3244041. DOI: 10.1084/jem.20110740. View

10.

Crotty S, Felgner P, Davies H, Glidewell J, Villarreal L, Ahmed R . Cutting edge: long-term B cell memory in humans after smallpox vaccination. J Immunol. 2003; 171(10):4969-73. DOI: 10.4049/jimmunol.171.10.4969. View

11.

Li S, Rouphael N, Duraisingham S, Romero-Steiner S, Presnell S, Davis C . Molecular signatures of antibody responses derived from a systems biology study of five human vaccines. Nat Immunol. 2013; 15(2):195-204. PMC: 3946932. DOI: 10.1038/ni.2789. View

12.

Odendahl M, Mei H, Hoyer B, Jacobi A, Hansen A, Muehlinghaus G . Generation of migratory antigen-specific plasma blasts and mobilization of resident plasma cells in a secondary immune response. Blood. 2004; 105(4):1614-21. DOI: 10.1182/blood-2004-07-2507. View

13.

Krzywinski M, Schein J, Birol I, Connors J, Gascoyne R, Horsman D . Circos: an information aesthetic for comparative genomics. Genome Res. 2009; 19(9):1639-45. PMC: 2752132. DOI: 10.1101/gr.092759.109. View

14.

Takemori T, Kaji T, Takahashi Y, Shimoda M, Rajewsky K . Generation of memory B cells inside and outside germinal centers. Eur J Immunol. 2014; 44(5):1258-64. DOI: 10.1002/eji.201343716. View

15.

Wrammert J, Smith K, Miller J, Langley W, Kokko K, Larsen C . Rapid cloning of high-affinity human monoclonal antibodies against influenza virus. Nature. 2008; 453(7195):667-71. PMC: 2515609. DOI: 10.1038/nature06890. View

16.

Singh H, Khan A, Dinner A . Gene regulatory networks in the immune system. Trends Immunol. 2014; 35(5):211-8. DOI: 10.1016/j.it.2014.03.006. View

17.

Ye J, Ma N, Madden T, Ostell J . IgBLAST: an immunoglobulin variable domain sequence analysis tool. Nucleic Acids Res. 2013; 41(Web Server issue):W34-40. PMC: 3692102. DOI: 10.1093/nar/gkt382. View

18.

Pinna D, Corti D, Jarrossay D, Sallusto F, Lanzavecchia A . Clonal dissection of the human memory B-cell repertoire following infection and vaccination. Eur J Immunol. 2009; 39(5):1260-70. PMC: 3864550. DOI: 10.1002/eji.200839129. View

19.

Lyon G, Mehta A, Varkey J, Brantly K, Plyler L, McElroy A . Clinical care of two patients with Ebola virus disease in the United States. N Engl J Med. 2014; 371(25):2402-9. DOI: 10.1056/NEJMoa1409838. View

20.

Tangye S, Tarlinton D . Memory B cells: effectors of long-lived immune responses. Eur J Immunol. 2009; 39(8):2065-75. DOI: 10.1002/eji.200939531. View