B1a Cells Play a Pathogenic Role in the Development of Autoimmune Arthritis

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Mar 26

PMID 27014914

Citations 22

Authors

Jun Deng

Xiaohui Wang

Qian Chen

Xiaoxuan Sun

Fan Xiao

King-Hung Ko

Miaojia Zhang

Liwei Lu

Affiliations

Soon will be listed here.

Abstract

Dysregulated functions of B1 cells have been implicated in the disease progression of various autoimmune disorders, but it remains largely unclear whether B1 cells are involved in the pathogenesis of autoimmune arthritis. In this study, we found that peritoneal B1a cells underwent proliferation and migrated to the inflamed joint tissue with upregulated RANKL expression during collagen-induced arthritis (CIA) development in mice. Adoptive transfer of B1a cells exacerbated arthritic severity and joint damage while intraperitoneal depletion of B1 cells ameliorated both arthritic symptoms and joint pathology in CIA mice. In culture, RANKL-expressing B1a cells significantly promoted the expansion of osteoclasts derived from bone marrow cells, which were in accord with the in vivo findings of increased osteoclastogenesis in CIA mice transferred with B1a cells. Together, these results have demonstrated a pathogenic role of B1a cells in the development of autoimmune arthritis through RANKL-mediated osteoclastogenesis.

Citing Articles

B-Cell and T-Cell Populations in Peripheral Blood Linked to Ocrelizumab Treatment Efficacy in Multiple Sclerosis.

Akbayir E, Ece A, Kizilay T, Tugce K, Ruziye E, Erol R In Vivo. 2025; 39(2):1162-1172.

PMID: 40010950 PMC: 11884471. DOI: 10.21873/invivo.13920.

IFN-I promotes T-cell-independent immunity and RBC autoantibodies via modulation of B-1 cell subsets in murine SCD.

Su S, Bao W, Liu Y, Shi P, Manwani D, Murakhovskaya I Blood. 2024; 145(3):334-347.

PMID: 39656114 PMC: 11775509. DOI: 10.1182/blood.2024025175.

Aberrant Activation of Immune and Non-Immune Cells Contributes to Joint Inflammation and Bone Degradation in Rheumatoid Arthritis.

Nandakumar K, Fang Q, Wingbro Agren I, Bejmo Z Int J Mol Sci. 2023; 24(21).

PMID: 37958864 PMC: 10648236. DOI: 10.3390/ijms242115883.

Sex Differences in the Frequencies of B and T Cell Subpopulations of Human Cord Blood.

Bous M, Schmitt C, Hans M, Weber R, Nourkami-Tutdibi N, Tenbruck S Int J Mol Sci. 2023; 24(14).

PMID: 37511278 PMC: 10380850. DOI: 10.3390/ijms241411511.

The mTORC1 pathway participate in hyper-function of B cells in immune thrombocytopenia.

Xiang Y, Liu L, Hou Y, Du S, Xu S, Zhou H Ann Hematol. 2023; 102(9):2317-2327.

PMID: 37421506 DOI: 10.1007/s00277-023-05348-6.

References

Yeo L, Toellner K, Salmon M, Filer A, Buckley C, Raza K . Cytokine mRNA profiling identifies B cells as a major source of RANKL in rheumatoid arthritis. Ann Rheum Dis. 2011; 70(11):2022-8. PMC: 3184241. DOI: 10.1136/ard.2011.153312. View

Labadi A, Balogh P . Differential preferences in serosal homing and distribution of peritoneal B-cell subsets revealed by in situ CFSE labeling. Int Immunol. 2009; 21(9):1047-56. DOI: 10.1093/intimm/dxp071. View

Maseda D, Candando K, Smith S, Kalampokis I, Weaver C, Plevy S . Peritoneal cavity regulatory B cells (B10 cells) modulate IFN-γ+CD4+ T cell numbers during colitis development in mice. J Immunol. 2013; 191(5):2780-2795. PMC: 3770313. DOI: 10.4049/jimmunol.1300649. View

Yeo L, Lom H, Juarez M, Snow M, Buckley C, Filer A . Expression of FcRL4 defines a pro-inflammatory, RANKL-producing B cell subset in rheumatoid arthritis. Ann Rheum Dis. 2014; 74(5):928-35. PMC: 4392201. DOI: 10.1136/annrheumdis-2013-204116. View

Silverman G, Carson D . Roles of B cells in rheumatoid arthritis. Arthritis Res Ther. 2004; 5 Suppl 4:S1-6. PMC: 2833442. DOI: 10.1186/ar1010. View

Enghard P, Humrich J, Chu V, Grussie E, Hiepe F, Burmester G . Class switching and consecutive loss of dsDNA-reactive B1a B cells from the peritoneal cavity during murine lupus development. Eur J Immunol. 2010; 40(6):1809-18. DOI: 10.1002/eji.200940050. View

Griffin D, Rothstein T . A small CD11b(+) human B1 cell subpopulation stimulates T cells and is expanded in lupus. J Exp Med. 2011; 208(13):2591-8. PMC: 3244038. DOI: 10.1084/jem.20110978. View

Yang H, Wang H, Ju Z, Ragab A, Lundback P, Long W . MD-2 is required for disulfide HMGB1-dependent TLR4 signaling. J Exp Med. 2015; 212(1):5-14. PMC: 4291531. DOI: 10.1084/jem.20141318. View

Zhong X, Lau S, Bai C, Degauque N, Holodick N, Steven S . A novel subpopulation of B-1 cells is enriched with autoreactivity in normal and lupus-prone mice. Arthritis Rheum. 2009; 60(12):3734-43. PMC: 2868318. DOI: 10.1002/art.25015. View

10.

Zhong X, Gao W, Degauque N, Bai C, Lu Y, Kenny J . Reciprocal generation of Th1/Th17 and T(reg) cells by B1 and B2 B cells. Eur J Immunol. 2007; 37(9):2400-4. DOI: 10.1002/eji.200737296. View

11.

Duan B, Morel L . Role of B-1a cells in autoimmunity. Autoimmun Rev. 2006; 5(6):403-8. DOI: 10.1016/j.autrev.2005.10.007. View

12.

Yenson V, Baumgarth N . Purification and immune phenotyping of B-1 cells from body cavities of mice. Methods Mol Biol. 2014; 1190:17-34. DOI: 10.1007/978-1-4939-1161-5_2. View

13.

Miranda-Carus M, Benito-Miguel M, Balsa A, Cobo-Ibanez T, Perez de Ayala C, Pascual-Salcedo D . Peripheral blood T lymphocytes from patients with early rheumatoid arthritis express RANKL and interleukin-15 on the cell surface and promote osteoclastogenesis in autologous monocytes. Arthritis Rheum. 2006; 54(4):1151-64. DOI: 10.1002/art.21731. View

14.

Stall A, Wells S, Lam K . B-1 cells: unique origins and functions. Semin Immunol. 1996; 8(1):45-59. DOI: 10.1006/smim.1996.0007. View

15.

Ishikawa S, Matsushima K . Aberrant B1 cell trafficking in a murine model for lupus. Front Biosci. 2006; 12:1790-803. DOI: 10.2741/2188. View

16.

Yang Y, Tung J, Ghosn E, Herzenberg L, Herzenberg L . Division and differentiation of natural antibody-producing cells in mouse spleen. Proc Natl Acad Sci U S A. 2007; 104(11):4542-6. PMC: 1838637. DOI: 10.1073/pnas.0700001104. View

17.

Diana J, Simoni Y, Furio L, Beaudoin L, Agerberth B, Barrat F . Crosstalk between neutrophils, B-1a cells and plasmacytoid dendritic cells initiates autoimmune diabetes. Nat Med. 2012; 19(1):65-73. DOI: 10.1038/nm.3042. View

18.

Ha S, Tsuji M, Suzuki K, Meek B, Yasuda N, Kaisho T . Regulation of B1 cell migration by signals through Toll-like receptors. J Exp Med. 2006; 203(11):2541-50. PMC: 2118139. DOI: 10.1084/jem.20061041. View

19.

Deng J, Liu Y, Yang M, Wang S, Zhang M, Wang X . Leptin exacerbates collagen-induced arthritis via enhancement of Th17 cell response. Arthritis Rheum. 2012; 64(11):3564-73. DOI: 10.1002/art.34637. View

20.

Dauphinee M, Tovar Z, Talal N . B cells expressing CD5 are increased in Sjögren's syndrome. Arthritis Rheum. 1988; 31(5):642-7. DOI: 10.1002/art.1780310509. View