Critical Requirement for BCR, BAFF, and BAFFR in Memory B Cell Survival

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2020 Oct 29

PMID 33119032

Citations 21

Authors

Jennifer Muller-Winkler

Richard Mitter

Julie C F Rappe

Lesley Vanes

Edina Schweighoffer

Hamid Mohammadi

Andreas Wack

Victor L J Tybulewicz

Affiliations

Soon will be listed here.

Abstract

Memory B cells (MBCs) are long-lived cells that form a critical part of immunological memory, providing rapid antibody responses to recurring infections. However, very little is known about signals controlling MBC survival. Previous work has shown that antigen is not required for MBC survival, but a requirement for the B cell antigen receptor (BCR) has not been tested. Other studies have shown that, unlike naive B cells, MBCs do not express BAFFR and their survival is independent of BAFF, the ligand for BAFFR. Here, using inducible genetic ablation, we show that survival of MBCs is critically dependent on the BCR and on signaling through the associated CD79A protein. Unexpectedly, we found that MBCs express BAFFR and that their survival requires BAFF and BAFFR; hence, loss of BAFF or BAFFR impairs recall responses. Finally, we show that MBC survival requires IKK2, a kinase that transduces BAFFR signals. Thus, MBC survival is critically dependent on signaling from BCR and BAFFR.

Citing Articles

Deciphering cell states and the cellular ecosystem to improve risk stratification in acute myeloid leukemia.

Zhang Z, Tang R, Zhu M, Zhu Z, Zhu J, Li H Brief Bioinform. 2025; 26(1).

PMID: 39865982 PMC: 11770069. DOI: 10.1093/bib/bbaf028.

Asparagine availability controls germinal center B cell homeostasis.

Yazicioglu Y, Marin E, Andrew H, Bentkowska K, Johnstone J, Mitchell R Sci Immunol. 2024; 9(102):eadl4613.

PMID: 39671468 PMC: 7617476. DOI: 10.1126/sciimmunol.adl4613.

The Latest Progress in the Application of Telitacicept in Autoimmune Diseases.

Liu B, Zhao Y, Liu D, Li X, Ma Z, Yang Q Drug Des Devel Ther. 2024; 18():5811-5825.

PMID: 39664967 PMC: 11633291. DOI: 10.2147/DDDT.S493923.

Characterization of class-switched B cells in chickens.

von La Roche D, Schumacher M, Kohn M, Trapp J, Schusser B, Rautenschlein S Front Immunol. 2024; 15:1484288.

PMID: 39640270 PMC: 11617357. DOI: 10.3389/fimmu.2024.1484288.

Simultaneous enhancement of cellular and humoral immunity by the lymph node-targeted cholesterolized TLR7 agonist liposomes.

Wan D, Bai Z, Zhang Y, Chen L, Que H, Lan T Acta Pharm Sin B. 2024; 14(10):4577-4590.

PMID: 39525596 PMC: 11544185. DOI: 10.1016/j.apsb.2024.06.006.

References

Rickert R, Jellusova J, Miletic A . Signaling by the tumor necrosis factor receptor superfamily in B-cell biology and disease. Immunol Rev. 2011; 244(1):115-33. PMC: 3202302. DOI: 10.1111/j.1600-065X.2011.01067.x. View

Hannum L, Haberman A, Anderson S, Shlomchik M . Germinal center initiation, variable gene region hypermutation, and mutant B cell selection without detectable immune complexes on follicular dendritic cells. J Exp Med. 2000; 192(7):931-42. PMC: 2193308. DOI: 10.1084/jem.192.7.931. View

Tangye S . Staying alive: regulation of plasma cell survival. Trends Immunol. 2011; 32(12):595-602. DOI: 10.1016/j.it.2011.09.001. View

Shinners N, Carlesso G, Castro I, Hoek K, Corn R, Woodland R . Bruton's tyrosine kinase mediates NF-kappa B activation and B cell survival by B cell-activating factor receptor of the TNF-R family. J Immunol. 2007; 179(6):3872-80. DOI: 10.4049/jimmunol.179.6.3872. View

Paramithiotis E, Cooper M . Memory B lymphocytes migrate to bone marrow in humans. Proc Natl Acad Sci U S A. 1997; 94(1):208-12. PMC: 19286. DOI: 10.1073/pnas.94.1.208. View

Cao X, Shores E, Hu-Li J, Anver M, Kelsall B, Russell S . Defective lymphoid development in mice lacking expression of the common cytokine receptor gamma chain. Immunity. 1995; 2(3):223-38. DOI: 10.1016/1074-7613(95)90047-0. View

Kaji T, Ishige A, Hikida M, Taka J, Hijikata A, Kubo M . Distinct cellular pathways select germline-encoded and somatically mutated antibodies into immunological memory. J Exp Med. 2012; 209(11):2079-97. PMC: 3478929. DOI: 10.1084/jem.20120127. View

Weisel F, Zuccarino-Catania G, Chikina M, Shlomchik M . A Temporal Switch in the Germinal Center Determines Differential Output of Memory B and Plasma Cells. Immunity. 2016; 44(1):116-130. PMC: 4724390. DOI: 10.1016/j.immuni.2015.12.004. View

Dogan I, Bertocci B, Vilmont V, Delbos F, Megret J, Storck S . Multiple layers of B cell memory with different effector functions. Nat Immunol. 2009; 10(12):1292-9. DOI: 10.1038/ni.1814. View

10.

Stohl W, Hiepe F, Latinis K, Thomas M, Scheinberg M, Clarke A . Belimumab reduces autoantibodies, normalizes low complement levels, and reduces select B cell populations in patients with systemic lupus erythematosus. Arthritis Rheum. 2012; 64(7):2328-37. PMC: 3350827. DOI: 10.1002/art.34400. View

11.

Engels N, Konig L, Schulze W, Radtke D, Vanshylla K, Lutz J . The immunoglobulin tail tyrosine motif upgrades memory-type BCRs by incorporating a Grb2-Btk signalling module. Nat Commun. 2014; 5:5456. PMC: 4263166. DOI: 10.1038/ncomms6456. View

12.

Jones D, Wilmore J, Allman D . Cellular Dynamics of Memory B Cell Populations: IgM+ and IgG+ Memory B Cells Persist Indefinitely as Quiescent Cells. J Immunol. 2015; 195(10):4753-9. PMC: 4637268. DOI: 10.4049/jimmunol.1501365. View

13.

Anderson S, Hannum L, Shlomchik M . Memory B cell survival and function in the absence of secreted antibody and immune complexes on follicular dendritic cells. J Immunol. 2006; 176(8):4515-9. DOI: 10.4049/jimmunol.176.8.4515. View

14.

Lutz J, Dittmann K, Bosl M, Winkler T, Wienands J, Engels N . Reactivation of IgG-switched memory B cells by BCR-intrinsic signal amplification promotes IgG antibody production. Nat Commun. 2016; 6:8575. PMC: 4633962. DOI: 10.1038/ncomms9575. View

15.

Park J, Greten F, Li Z, Karin M . Macrophage apoptosis by anthrax lethal factor through p38 MAP kinase inhibition. Science. 2002; 297(5589):2048-51. DOI: 10.1126/science.1073163. View

16.

Sonoda E, Pewzner-Jung Y, Schwers S, Taki S, Jung S, Eilat D . B cell development under the condition of allelic inclusion. Immunity. 1997; 6(3):225-33. DOI: 10.1016/s1074-7613(00)80325-8. View

17.

Tokoyoda K, Egawa T, Sugiyama T, Choi B, Nagasawa T . Cellular niches controlling B lymphocyte behavior within bone marrow during development. Immunity. 2004; 20(6):707-18. DOI: 10.1016/j.immuni.2004.05.001. View

18.

Giesecke C, Frolich D, Reiter K, Mei H, Wirries I, Kuhly R . Tissue distribution and dependence of responsiveness of human antigen-specific memory B cells. J Immunol. 2014; 192(7):3091-100. DOI: 10.4049/jimmunol.1302783. View

19.

Anderson S, Tomayko M, Ahuja A, Haberman A, Shlomchik M . New markers for murine memory B cells that define mutated and unmutated subsets. J Exp Med. 2007; 204(9):2103-14. PMC: 2118690. DOI: 10.1084/jem.20062571. View

20.

Vieira P, Rajewsky K . Persistence of memory B cells in mice deprived of T cell help. Int Immunol. 1990; 2(6):487-94. DOI: 10.1093/intimm/2.6.487. View