IMMUNE NETWORK

The Korean Association of Immunobiologists (대한면역학회)
권호 표지
DOI QR코드

DOI QR Code

Increased B Cell Understanding Puts Improved Vaccine Platforms Just Over the Horizon

  • Geneva Rose Notario (Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine) ;
  • Kihyuck Kwak (Institute for Immunology and Immunological Diseases, Brain Korea 21 PLUS Project for Medical Science, Yonsei University College of Medicine)
  • Received : 2022.06.15
  • Accepted : 2022.11.08
  • Published : 2022.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

In the face of an endlessly expanding repertoire of Ags, vaccines are constantly being tested, each more effective than the last. As viruses and other pathogens evolve to become more infectious, the need for efficient and effective vaccines grows daily, which is especially obvious in an era that is still attempting to remove itself from the clutches of the severe acute respiratory syndrome coronavirus 2, the cause of coronavirus pandemic. To continue evolving alongside these pathogens, it is proving increasingly essential to consider one of the main effector cells of the immune system. As one of the chief orchestrators of the humoral immune response, the B cell and other lymphocytes are essential to not only achieving immunity, but also maintaining it, which is the vital objective of every vaccine.

Keywords

Acknowledgement

All figures are created with Biorender.com.

References

  1. Elsner RA, Shlomchik MJ. Germinal center and extrafollicular B cell responses in vaccination, immunity, and autoimmunity. Immunity 2020;53:1136-1150.
  2. Allman D, Wilmore JR, Gaudette BT. The continuing story of T-cell independent antibodies. Immunol Rev 2019;288:128-135.
  3. He JS, Subramaniam S, Narang V, Srinivasan K, Saunders SP, Carbajo D, Wen-Shan T, Hidayah Hamadee N, Lum J, Lee A, et al. IgG1 memory B cells keep the memory of IgE responses. Nat Commun 2017;8:641.
  4. Boonyaratanakornkit J, Taylor JJ. Techniques to study antigen-specific B cell responses. Front Immunol 2019;10:1694.
  5. Giannotta G, Giannotta N. mRNA COVID-19 vaccines and long-lived plasma cells: a complicated relationship. Vaccines (Basel) 2021;9:1503.
  6. Baker SC. Coronaviruses: from common colds to severe acute respiratory syndrome. Pediatr Infect Dis J 2004;23:1049-1050.
  7. Turner JS, Kim W, Kalaidina E, Goss CW, Rauseo AM, Schmitz AJ, Hansen L, Haile A, Klebert MK, Pusic I, et al. SARS-CoV-2 infection induces long-lived bone marrow plasma cells in humans. Nature 2021;595:421-425.
  8. Laidlaw BJ, Ellebedy AH. The germinal centre B cell response to SARS-CoV-2. Nat Rev Immunol 2022;22:7-18.
  9. Pape KA, Dileepan T, Kabage AJ, Kozysa D, Batres R, Evert C, Matson M, Lopez S, Krueger PD, Graiziger C, et al. High-affinity memory B cells induced by SARS-CoV-2 infection produce more plasmablasts and atypical memory B cells than those primed by mRNA vaccines. Cell Reports 2021;37:109823.
  10. Guthmiller JJ, Utset HA, Wilson PC. B cell responses against influenza viruses: short-lived humoral immunity against a life-long threat. Viruses 2021;13:965.
  11. Garcia-Beltran WF, St Denis KJ, Hoelzemer A, Lam EC, Nitido AD, Sheehan ML, Berrios C, Ofoman O, Chang CC, Hauser BM, et al. mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell 2022;185:457-466.e4.
  12. Pape KA, Maul RW, Dileepan T, Paustian AS, Gearhart PJ, Jenkins MK. Naive B cells with high-avidity germline-encoded antigen receptors produce persistent IgM+ and transient IgG+ memory B cells. Immunity 2018;48:1135-1143.e4.
  13. Weill JC, Reynaud CA. IgM memory B cells: specific effectors of innate-like and adaptive responses. Curr Opin Immunol 2020;63:1-6.
  14. Mesin L, Schiepers A, Ersching J, Barbulescu A, Cavazzoni CB, Angelini A, Okada T, Kurosaki T, Victora GD. Restricted clonality and limited germinal center reentry characterize memory B cell reactivation by boosting. Cell 2020;180:92-106.e11.
  15. Viant C, Weymar GH, Escolano A, Chen S, Hartweger H, Cipolla M, Gazumyan A, Nussenzweig MC. Antibody affinity shapes the choice between memory and germinal center B cell fates. Cell 2020;183:1298-1311.e11.
  16. Baumgarth N. The shaping of a B cell pool maximally responsive to infections. Annu Rev Immunol 2021;39:103-129.
  17. Ionescu L, Urschel S. Memory B cells and long-lived plasma cells. Transplantation 2019;103:890-898.
  18. Krautler NJ, Suan D, Butt D, Bourne K, Hermes JR, Chan TD, Sundling C, Kaplan W, Schofield P, Jackson J, et al. Differentiation of germinal center B cells into plasma cells is initiated by high-affinity antigen and completed by Tfh cells. J Exp Med 2017;214:1259-1267.
  19. Ottens K, Hinman RM, Barrios E, Skaug B, Davis LS, Li QZ, Castrillon DH, Satterthwaite AB. Foxo3 promotes apoptosis of B cell receptor-stimulated immature B cells, thus limiting the window for receptor editing. J Immunol 2018;201:940-949.
  20. Kelly LM, Pereira JP, Yi T, Xu Y, Cyster JG. EBI2 guides serial movements of activated B cells and ligand activity is detectable in lymphoid and nonlymphoid tissues. J Immunol 2011;187:3026-3032.
  21. Glaros V, Rauschmeier R, Artemov AV, Reinhardt A, Ols S, Emmanouilidi A, Gustafsson C, You Y, Mirabello C, Bjorklund AK, et al. Limited access to antigen drives generation of early B cell memory while restraining the plasmablast response. Immunity 2021;54:2005-2023.e10.
  22. Carrasco YR, Batista FD. B cell recognition of membrane-bound antigen: an exquisite way of sensing ligands. Curr Opin Immunol 2006;18:286-291.
  23. Shlomchik MJ, Luo W, Weisel F. Linking signaling and selection in the germinal center. Immunol Rev 2019;288:49-63.
  24. Gutzeit C, Chen K, Cerutti A. The enigmatic function of IgD: some answers at last. Eur J Immunol 2018;48:1101-1113.
  25. Luo W, Hawse W, Conter L, Trivedi N, Weisel F, Wikenheiser D, Cattley RT, Shlomchik MJ. The AKT kinase signaling network is rewired by PTEN to control proximal BCR signaling in germinal center B cells. Nat Immunol 2019;20:736-746.
  26. Nakagawa R, Calado DP. Positive selection in the light zone of germinal centers. Front Immunol 2021;12:661678.
  27. Sabouri Z, Perotti S, Spierings E, Humburg P, Yabas M, Bergmann H, Horikawa K, Roots C, Lambe S, Young C, et al. IgD attenuates the IgM-induced anergy response in transitional and mature B cells. Nat Commun 2016;7:13381.
  28. Bretscher PA, Al-Yassin GA. On how the immune system preferentially interacts with antigen-specific molecules bound to antigen over unbound molecules, with emphasis on B cell receptor signalling. Scand J Immunol 2019;90:e12795-e12795.
  29. Gold MR, Reth MG. Antigen receptor function in the context of the nanoscale organization of the B cell membrane. Annu Rev Immunol 2019;37:97-123.
  30. Ripperger TJ, Bhattacharya D. Transcriptional and metabolic control of memory B cells and plasma cells. Annu Rev Immunol 2021;39:345-368.
  31. Laidlaw BJ, Cyster JG. Transcriptional regulation of memory B cell differentiation. Nat Rev Immunol 2021;21:209-220.
  32. Akkaya M, Kwak K, Pierce SK. B cell memory: building two walls of protection against pathogens. Nat Rev Immunol 2020;20:229-238.
  33. Akkaya M, Akkaya B, Kim AS, Miozzo P, Sohn H, Pena M, Roesler AS, Theall BP, Henke T, Kabat J, et al. Toll-like receptor 9 antagonizes antibody affinity maturation. Nat Immunol 2018;19:255-266.
  34. Meyer SJ, Steffensen M, Acs A, Weisenburger T, Wadewitz C, Winkler TH, Nitschke L. CD22 controls germinal center B cell receptor signaling, which influences plasma cell and memory B cell output. J Immunol 2021;207:1018-1032.
  35. Grosche L, Knippertz I, Konig C, Royzman D, Wild AB, Zinser E, Sticht H, Muller YA, Steinkasserer A, Lechmann M. The CD83 molecule - an important immune checkpoint. Front Immunol 2020;11:721.
  36. Castiblanco DP, Maul RW, Russell Knode LM, Gearhart PJ. Co-stimulation of BCR and Toll-like receptor 7 increases somatic hypermutation, memory B cell formation, and secondary antibody response to protein antigen. Front Immunol 2017;8:1833.
  37. Kennedy DE, Okoreeh MK, Maienschein-Cline M, Ai J, Veselits M, McLean KC, Dhungana Y, Wang H, Peng J, Chi H, et al. Novel specialized cell state and spatial compartments within the germinal center. Nat Immunol 2020;21:660-670.
  38. Dominguez-Sola D, Victora GD, Ying CY, Phan RT, Saito M, Nussenzweig MC, Dalla-Favera R. The proto-oncogene MYC is required for selection in the germinal center and cyclic reentry. Nat Immunol 2012;13:1083-1091.
  39. Calado DP, Sasaki Y, Godinho SA, Pellerin A, Kochert K, Sleckman BP, de Alboran IM, Janz M, Rodig S, Rajewsky K. The cell-cycle regulator c-Myc is essential for the formation and maintenance of germinal centers. Nat Immunol 2012;13:1092-1100.
  40. Sundling C, Lau AW, Bourne K, Young C, Laurianto C, Hermes JR, Menzies RJ, Butt D, Krautler NJ, Zahra D, et al. Positive selection of IgG+ over IgM+ B cells in the germinal center reaction. Immunity 2021;54:988-1001.e5.
  41. Roco JA, Mesin L, Binder SC, Nefzger C, Gonzalez-Figueroa P, Canete PF, Ellyard J, Shen Q, Robert PA, Cappello J, et al. Class-switch recombination occurs infrequently in germinal centers. Immunity 2019;51:337-350.e7.
  42. Toboso-Navasa A, Gunawan A, Morlino G, Nakagawa R, Taddei A, Damry D, Patel Y, Chakravarty P, Janz M, Kassiotis G, et al. Restriction of memory B cell differentiation at the germinal center B cell positive selection stage. J Exp Med 2020;217:e20191933.
  43. Cancro MP, Tomayko MM. Memory B cells and plasma cells: the differentiative continuum of humoral immunity. Immunol Rev 2021;303:72-82.
  44. Viant C, Wirthmiller T, ElTanbouly MA, Chen ST, Cipolla M, Ramos V, Oliveira TY, Stamatatos L, Nussenzweig MC. Germinal center-dependent and -independent memory B cells produced throughout the immune response. J Exp Med 2021;218:e20202489.
  45. Duan L, Liu D, Chen H, Mintz MA, Chou MY, Kotov DI, Xu Y, An J, Laidlaw BJ, Cyster JG. Follicular dendritic cells restrict interleukin-4 availability in germinal centers and foster memory B cell generation. Immunity 2021;54:2256-2272.e6.
  46. Kenderes KJ, Levack RC, Papillion AM, Cabrera-Martinez B, Dishaw LM, Winslow GM. T-bet+ IgM memory cells generate multi-lineage effector B cells. Cell Reports 2018;24:824-837.e3.
  47. Koike T, Harada K, Horiuchi S, Kitamura D. The quantity of CD40 signaling determines the differentiation of B cells into functionally distinct memory cell subsets. eLife 2019;8:e44245.
  48. Turner JS, Benet ZL, Grigorova I. Transiently antigen primed B cells can generate multiple subsets of memory cells. PLoS One 2017;12:e0183877.
  49. Golinski ML, Demeules M, Derambure C, Riou G, Maho-Vaillant M, Boyer O, Joly P, Calbo S. CD11c+ B cells are mainly memory cells, precursors of antibody secreting cells in healthy donors. Front Immunol 2020;11:32.
  50. Phan TG, Tangye SG. Memory B cells: total recall. Curr Opin Immunol 2017;45:132-140.
  51. Khodadadi L, Cheng Q, Radbruch A, Hiepe F. The maintenance of memory plasma cells. Front Immunol 2019;10:721.
  52. Limon JJ, Fruman DA. Akt and mTOR in B cell activation and differentiation. Front Immunol 2012;3:228.
  53. Lam WY, Bhattacharya D. Metabolic links between plasma cell survival, secretion, and stress. Trends Immunol 2018;39:19-27.
  54. Tellier J, Shi W, Minnich M, Liao Y, Crawford S, Smyth GK, Kallies A, Busslinger M, Nutt SL. Blimp-1 controls plasma cell function through the regulation of immunoglobulin secretion and the unfolded protein response. Nat Immunol 2016;17:323-330.
  55. Keating R, Hertz T, Wehenkel M, Harris TL, Edwards BA, McClaren JL, Brown SA, Surman S, Wilson ZS, Bradley P, et al. The kinase mTOR modulates the antibody response to provide cross-protective immunity to lethal infection with influenza virus. Nat Immunol 2013;14:1266-1276.
  56. Brynjolfsson SF, Mohaddes M, Karrholm J, Wick MJ. Long-lived plasma cells in human bone marrow can be either CD19+ or CD19. Blood Adv 2017;1:835-838.
  57. Hammarlund E, Thomas A, Amanna IJ, Holden LA, Slayden OD, Park B, Gao L, Slifka MK. Plasma cell survival in the absence of B cell memory. Nat Commun 2017;8:1781.
  58. Pape KA, Jenkins MK. Do memory B cells form secondary germinal centers?: it depends. Cold Spring Harb Perspect Biol 2018;10:a029116.
  59. Gitlin AD, von Boehmer L, Gazumyan A, Shulman Z, Oliveira TY, Nussenzweig MC. Independent roles of switching and hypermutation in the development and persistence of B lymphocyte memory. Immunity 2016;44:769-781.
  60. Lavelle EC, Ward RW. Mucosal vaccines - fortifying the frontiers. Nat Rev Immunol 2022;22:236-250.
  61. Allie SR, Bradley JE, Mudunuru U, Schultz MD, Graf BA, Lund FE, Randall TD. The establishment of resident memory B cells in the lung requires local antigen encounter. Nat Immunol 2019;20:97-108.
  62. Barker KA, Etesami NS, Shenoy AT, Arafa EI, Lyon de Ana C, Smith NM, Martin IM, Goltry WN, Barron AM, Browning JL, et al. Lung-resident memory B cells protect against bacterial pneumonia. J Clin Invest 2021;131:e141810.
  63. Bricker TL, Darling TL, Hassan AO, Harastani HH, Soung A, Jiang X, Dai YN, Zhao H, Adams LJ, Holtzman MJ, et al. A single intranasal or intramuscular immunization with chimpanzee adenovirus-vectored SARS-CoV-2 vaccine protects against pneumonia in hamsters. Cell Reports 2021;36:109400.
  64. Woodruff MC, Ramonell RP, Haddad NS, Anam FA, Rudolph ME, Walker TA, Truong AD, Dixit AN, Han JE, Cabrera-Mora M, et al. Dysregulated naive B cells and de novo autoreactivity in severe COVID-19. Nature 2022;611:139-147.
  65. Reed SG, Orr MT, Fox CB. Key roles of adjuvants in modern vaccines. Nat Med 2013;19:1597-1608.
  66. Pulendran B, S Arunachalam P, O'Hagan DT. Emerging concepts in the science of vaccine adjuvants. Nat Rev Drug Discov 2021;20:454-475.
  67. Kato Y, Abbott RK, Freeman BL, Haupt S, Groschel B, Silva M, Menis S, Irvine DJ, Schief WR, Crotty S. Multifaceted effects of antigen valency on B cell response composition and differentiation in vivo. Immunity 2020;53:548-563.e8.
  68. Cirelli KM, Carnathan DG, Nogal B, Martin JT, Rodriguez OL, Upadhyay AA, Enemuo CA, Gebru EH, Choe Y, Viviano F, et al. Slow delivery immunization enhances HIV neutralizing antibody and germinal center responses via modulation of immunodominance. Cell 2019;177:1153-1171.e28.
  69. Andrews SF, Huang Y, Kaur K, Popova LI, Ho IY, Pauli NT, Henry Dunand CJ, Taylor WM, Lim S, Huang M, et al. Immune history profoundly affects broadly protective B cell responses to influenza. Sci Transl Med 2015;7:316ra192.
  70. Finlay BB, McFadden G. Anti-immunology: evasion of the host immune system by bacterial and viral pathogens. Cell 2006;124:767-782.