B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting

Overview

Journal Cell Rep

Publisher Cell Press

Specialties Biology
Cell Biology
Molecular Biology

Date 2018 Nov 8

PMID 30403996

Citations 21

Authors

Jackson Steed Turner

Fang Ke

Irina Leonidovna Grigorova

Affiliations

Soon will be listed here.

Abstract

Antigen-dependent engagement of germinal center (GC) B cell receptors (BCRs) promotes antigen internalization and presentation for follicular helper T cells. However, whether BCR signaling is critical or synergistic with T cell help for GC B cell selection or differentiation is unclear. Here, by adapting an experimental approach that enables independent delivery of BCR-crosslinking antigen or T cell help to GC B cells in vivo, we showed that T cell help was sufficient to induce GC B cell expansion and plasmablast formation. However, although BCR crosslinking could not by itself promote GC B cell selection or differentiation, it could synergize with T cell help to enhance the GC and plasmablast responses when T cell help was limiting. These findings indicate that GC B cells can integrate variable inputs from T cell help and BCR signaling in vivo for an optimal process of selection and differentiation, critical for potent long-term humoral immunity.

Citing Articles

Role of tertiary lymphoid structures and B cells in clinical immunotherapy of gastric cancer.

Chen W, Zhang L, Gao M, Zhang N, Wang R, Liu Y Front Immunol. 2025; 15():1519034.

PMID: 39840050 PMC: 11747648. DOI: 10.3389/fimmu.2024.1519034.

Defective germinal center selection results in persistence of self-reactive B cells from the primary to the secondary repertoire in Primary Antiphospholipid Syndrome.

Dieudonne Y, Lorenzetti R, Rottura J, Janowska I, Frenger Q, Jacquel L Nat Commun. 2024; 15(1):9921.

PMID: 39548093 PMC: 11568317. DOI: 10.1038/s41467-024-54228-8.

Tertiary lymphoid structures in diseases: immune mechanisms and therapeutic advances.

Zhao L, Jin S, Wang S, Zhang Z, Wang X, Chen Z Signal Transduct Target Ther. 2024; 9(1):225.

PMID: 39198425 PMC: 11358547. DOI: 10.1038/s41392-024-01947-5.

Antigen-Clustered Nanovaccine Achieves Long-Term Tumor Remission by Promoting B/CD 4 T Cell Crosstalk.

Li C, Clauson R, Bugada L, Ke F, He B, Yu Z ACS Nano. 2024; 18(13):9584-9604.

PMID: 38513119 PMC: 11130742. DOI: 10.1021/acsnano.3c13038.

Biomaterial engineering strategies for B cell immunity modulations.

Zareein A, Mahmoudi M, Jadhav S, Wilmore J, Wu Y Biomater Sci. 2024; 12(8):1981-2006.

PMID: 38456305 PMC: 11019864. DOI: 10.1039/d3bm01841e.

References

Goenka R, Matthews A, Zhang B, ONeill P, Scholz J, Migone T . Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation. J Exp Med. 2013; 211(1):45-56. PMC: 3892970. DOI: 10.1084/jem.20130505. View

Barnden M, Allison J, Heath W, Carbone F . Defective TCR expression in transgenic mice constructed using cDNA-based alpha- and beta-chain genes under the control of heterologous regulatory elements. Immunol Cell Biol. 1998; 76(1):34-40. DOI: 10.1046/j.1440-1711.1998.00709.x. View

Chan T, Wood K, Hermes J, Butt D, Jolly C, Basten A . Elimination of germinal-center-derived self-reactive B cells is governed by the location and concentration of self-antigen. Immunity. 2012; 37(5):893-904. DOI: 10.1016/j.immuni.2012.07.017. View

Shokat K, Goodnow C . Antigen-induced B-cell death and elimination during germinal-centre immune responses. Nature. 1995; 375(6529):334-8. DOI: 10.1038/375334a0. View

Allen C, Okada T, Tang H, Cyster J . Imaging of germinal center selection events during affinity maturation. Science. 2006; 315(5811):528-31. DOI: 10.1126/science.1136736. View

Ding B, Bi E, Chen H, Yu J, Ye B . IL-21 and CD40L synergistically promote plasma cell differentiation through upregulation of Blimp-1 in human B cells. J Immunol. 2013; 190(4):1827-36. PMC: 3563840. DOI: 10.4049/jimmunol.1201678. View

Turner J, Marthi M, Benet Z, Grigorova I . Transiently antigen-primed B cells return to naive-like state in absence of T-cell help. Nat Commun. 2017; 8:15072. PMC: 5413946. DOI: 10.1038/ncomms15072. View

Rookhuizen D, DeFranco A . Toll-like receptor 9 signaling acts on multiple elements of the germinal center to enhance antibody responses. Proc Natl Acad Sci U S A. 2014; 111(31):E3224-33. PMC: 4128120. DOI: 10.1073/pnas.1323985111. View

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

10.

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

11.

Garin A, Meyer-Hermann M, Contie M, Figge M, Buatois V, Gunzer M . Toll-like receptor 4 signaling by follicular dendritic cells is pivotal for germinal center onset and affinity maturation. Immunity. 2010; 33(1):84-95. DOI: 10.1016/j.immuni.2010.07.005. View

12.

Khalil A, Cambier J, Shlomchik M . B cell receptor signal transduction in the GC is short-circuited by high phosphatase activity. Science. 2012; 336(6085):1178-81. PMC: 3777391. DOI: 10.1126/science.1213368. View

13.

Luo W, Weisel F, Shlomchik M . B Cell Receptor and CD40 Signaling Are Rewired for Synergistic Induction of the c-Myc Transcription Factor in Germinal Center B Cells. Immunity. 2018; 48(2):313-326.e5. PMC: 5821563. DOI: 10.1016/j.immuni.2018.01.008. View

14.

Turner J, Benet Z, Grigorova I . Transiently antigen primed B cells can generate multiple subsets of memory cells. PLoS One. 2017; 12(8):e0183877. PMC: 5574538. DOI: 10.1371/journal.pone.0183877. View

15.

Krautler N, Suan D, Butt D, Bourne K, Hermes J, Chan T . 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(5):1259-1267. PMC: 5413338. DOI: 10.1084/jem.20161533. View

16.

Pulendran B, Kannourakis G, Nouri S, Smith K, Nossal G . Soluble antigen can cause enhanced apoptosis of germinal-centre B cells. Nature. 1995; 375(6529):331-4. DOI: 10.1038/375331a0. View

17.

Silver J, Zuo T, Chaudhary N, Kumari R, Tong P, Giguere S . Stochasticity enables BCR-independent germinal center initiation and antibody affinity maturation. J Exp Med. 2017; 215(1):77-90. PMC: 5748855. DOI: 10.1084/jem.20171022. View

18.

Han S, Hathcock K, Zheng B, Kepler T, Hodes R, Kelsoe G . Cellular interaction in germinal centers. Roles of CD40 ligand and B7-2 in established germinal centers. J Immunol. 1995; 155(2):556-67. View

19.

Bannard O, McGowan S, Ersching J, Ishido S, Victora G, Shin J . Ubiquitin-mediated fluctuations in MHC class II facilitate efficient germinal center B cell responses. J Exp Med. 2016; 213(6):993-1009. PMC: 4886361. DOI: 10.1084/jem.20151682. View

20.

Victoratos P, Lagnel J, Tzima S, Alimzhanov M, Rajewsky K, Pasparakis M . FDC-specific functions of p55TNFR and IKK2 in the development of FDC networks and of antibody responses. Immunity. 2006; 24(1):65-77. DOI: 10.1016/j.immuni.2005.11.013. View