Synchronous Germinal Center Onset Impacts the Efficiency of Antibody Responses

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2019 Sep 27

PMID 31555300

Citations 12

Authors

Theinmozhi Arulraj

Sebastian C Binder

Philippe A Robert

Michael Meyer-Hermann

Affiliations

Soon will be listed here.

Abstract

The germinal center reaction is an important target for modulating antibody responses. Antibody production from germinal centers is regulated by a negative feedback mechanism termed antibody feedback. By imposing antibody feedback, germinal centers can interact and regulate the output of other germinal centers. Using an agent-based model of the germinal center reaction, we studied the impact of antibody feedback on kinetics and efficiency of a germinal center. Our simulations predict that high feedback of antibodies from germinal centers reduces the production of plasma cells and subsequently the efficiency of the germinal center reaction by promoting earlier termination. Affinity maturation is only weakly improved by increased antibody feedback and ultimately interrupted because of premature termination of the reaction. The model predicts that the asynchronous onset and changes in number of germinal centers could alter the efficiency of antibody response due to changes in feedback by soluble antibodies. Consequently, late initialized germinal centers have a compromised output due to higher antibody feedback from the germinal centers formed earlier. The results demonstrate potential effects of germinal center intercommunication and highlight the importance of understanding germinal center interactions for optimizing the antibody response, in particular, in the elderly and in the context of vaccination.

Citing Articles

Maturation of germinal center B cells after influenza virus vaccination in humans.

McIntire K, Meng H, Lin T, Kim W, Moore N, Han J J Exp Med. 2024; 221(8).

PMID: 38935072 PMC: 11211068. DOI: 10.1084/jem.20240668.

High affinity mAb infusion can enhance maximum affinity maturation during HIV Env immunization.

Thomas P, Rees-Spear C, Griffith S, Muir L, Touizer E, Andrabi R iScience. 2024; 27(4):109495.

PMID: 38550978 PMC: 10973984. DOI: 10.1016/j.isci.2024.109495.

Soluble ACE2 correlates with severe COVID-19 and can impair antibody responses.

Lebedin M, Ratswohl C, Garg A, Schips M, Garcia C, Spatt L iScience. 2024; 27(3):109330.

PMID: 38496296 PMC: 10940809. DOI: 10.1016/j.isci.2024.109330.

Convergent evolution and B-cell recirculation in germinal centers in a human lymph node.

Pelissier A, Stratigopoulou M, Donner N, Dimitriadis E, Bende R, Guikema J Life Sci Alliance. 2023; 6(11).

PMID: 37640448 PMC: 10462906. DOI: 10.26508/lsa.202301959.

Spatial dysregulation of T follicular helper cells impairs vaccine responses in aging.

Silva-Cayetano A, Fra-Bido S, Robert P, Innocentin S, Burton A, Watson E Nat Immunol. 2023; 24(7):1124-1137.

PMID: 37217705 PMC: 10307630. DOI: 10.1038/s41590-023-01519-9.

References

Karlsson M, Wernersson S, Diaz De Stahl T, Gustavsson S, Heyman B . Efficient IgG-mediated suppression of primary antibody responses in Fcgamma receptor-deficient mice. Proc Natl Acad Sci U S A. 1999; 96(5):2244-9. PMC: 26768. DOI: 10.1073/pnas.96.5.2244. View

Kesmir C, de Boer R . A mathematical model on germinal center kinetics and termination. J Immunol. 1999; 163(5):2463-9. View

Heyman B . Regulation of antibody responses via antibodies, complement, and Fc receptors. Annu Rev Immunol. 2000; 18:709-37. DOI: 10.1146/annurev.immunol.18.1.709. View

Streilein J, Read C . A mathematical model in immunoregulation where the spleen has a pivotal role. J Theor Biol. 1976; 61(2):363-76. DOI: 10.1016/0022-5193(76)90024-2. View

Rao S, Vora K, Manser T . Differential expression of the inhibitory IgG Fc receptor FcgammaRIIB on germinal center cells: implications for selection of high-affinity B cells. J Immunol. 2002; 169(4):1859-68. DOI: 10.4049/jimmunol.169.4.1859. View

Aydar Y, Balogh P, Tew J, Szakal A . Altered regulation of Fc gamma RII on aged follicular dendritic cells correlates with immunoreceptor tyrosine-based inhibition motif signaling in B cells and reduced germinal center formation. J Immunol. 2003; 171(11):5975-87. DOI: 10.4049/jimmunol.171.11.5975. View

Shortman K, Lahoud M, Caminschi I . Improving vaccines by targeting antigens to dendritic cells. Exp Mol Med. 2009; 41(2):61-6. PMC: 2679330. DOI: 10.3858/emm.2009.41.2.008. View

Sallusto F, Lanzavecchia A, Araki K, Ahmed R . From vaccines to memory and back. Immunity. 2010; 33(4):451-63. PMC: 3760154. DOI: 10.1016/j.immuni.2010.10.008. View

Victora G, Schwickert T, Fooksman D, Kamphorst A, Meyer-Hermann M, Dustin M . Germinal center dynamics revealed by multiphoton microscopy with a photoactivatable fluorescent reporter. Cell. 2010; 143(4):592-605. PMC: 3035939. DOI: 10.1016/j.cell.2010.10.032. View

10.

Kasturi S, Skountzou I, Albrecht R, Koutsonanos D, Hua T, Nakaya H . Programming the magnitude and persistence of antibody responses with innate immunity. Nature. 2011; 470(7335):543-7. PMC: 3057367. DOI: 10.1038/nature09737. View

11.

Pulendran B, Ahmed R . Immunological mechanisms of vaccination. Nat Immunol. 2011; 12(6):509-17. PMC: 3253344. DOI: 10.1038/ni.2039. View

12.

Victora G, Nussenzweig M . Germinal centers. Annu Rev Immunol. 2012; 30:429-57. DOI: 10.1146/annurev-immunol-020711-075032. View

13.

Meyer-Hermann M, Mohr E, Pelletier N, Zhang Y, Victora G, Toellner K . A theory of germinal center B cell selection, division, and exit. Cell Rep. 2012; 2(1):162-74. DOI: 10.1016/j.celrep.2012.05.010. View

14.

Zhang Y, Meyer-Hermann M, George L, Figge M, Khan M, Goodall M . Germinal center B cells govern their own fate via antibody feedback. J Exp Med. 2013; 210(3):457-64. PMC: 3600904. DOI: 10.1084/jem.20120150. View

15.

Szakal A, Taylor J, Smith J, Kosco M, Burton G, Tew J . Kinetics of germinal center development in lymph nodes of young and aging immune mice. Anat Rec. 1990; 227(4):475-85. DOI: 10.1002/ar.1092270411. View

16.

Mackey M, Maini P . What has mathematics done for biology?. Bull Math Biol. 2015; 77(5):735-8. DOI: 10.1007/s11538-015-0065-9. View

17.

Wiedermann U, Garner-Spitzer E, Wagner A . Primary vaccine failure to routine vaccines: Why and what to do?. Hum Vaccin Immunother. 2016; 12(1):239-43. PMC: 4962729. DOI: 10.1080/21645515.2015.1093263. View

18.

Tas J, Mesin L, Pasqual G, Targ S, Jacobsen J, Mano Y . Visualizing antibody affinity maturation in germinal centers. Science. 2016; 351(6277):1048-54. PMC: 4938154. DOI: 10.1126/science.aad3439. View

19.

Linterman M, Hill D . Can follicular helper T cells be targeted to improve vaccine efficacy?. F1000Res. 2016; 5. PMC: 4784016. DOI: 10.12688/f1000research.7388.1. View

20.

Castro M, Lythe G, Molina-Paris C, Ribeiro R . Mathematics in modern immunology. Interface Focus. 2016; 6(2):20150093. PMC: 4759751. DOI: 10.1098/rsfs.2015.0093. View