B Cell Subsets and Dysfunction of Regulatory B Cells in IgG4-related Diseases and Primary Sjögren's Syndrome: the Similarities and Differences

Overview

Journal Arthritis Res Ther

Publisher Biomed Central

Specialty Rheumatology

Date 2014 Jun 3

PMID 24887143

Citations 37

Authors

Wei Lin

Lixia Jin

Hua Chen

Qingjun Wu

Yunyun Fei

Wenjie Zheng

Qian Wang

Ping Li

Yongzhe Li

Wen Zhang

Yan Zhao

Xiaofeng Zeng

Fengchun Zhang

Affiliations

Soon will be listed here.

Abstract

Introduction: IgG4-related disease (IgG4-RD) is a multisystem-involved autoimmune disease. Abnormally activated and differentiated B cells may play important roles. Regulatory B cells (Breg) are newly defined B cell subgroups with immunosuppressive functions. In this study, we investigated the differences of B cell subsets, the expressions of co-stimulatory molecules on B cells, and the function of Breg cells in patients with IgG4-RD, primary Sjögren's syndrome (pSS) as well as in healthy controls (HC).

Methods: Newly diagnosed IgG4-RD patients (n = 48) were enrolled, 38 untreated pSS patients and 30 healthy volunteers were recruited as disease and healthy controls. To analyze B cell subsets and B cell activity, PBMCs were surface stained and detected by flow cytometry. The function of Breg cells was tested by coculturing isolated CD19 + CD24(hi)CD38(hi) Breg cells with purified CD4 + CD25- T cells. Serum cytokines were measured by ELISA and cytometric bead array. Relationship between clinical data and laboratory findings were analyzed as well.

Results: Compared with pSS patients and HC, IgG4-RD patients had a lower frequency of peripheral Breg cells. Interestingly, CD19 + CD24-CD38(hi) B cell subsets were significantly higher in peripheral B cells from IgG4-RD patients than in pSS patients and HC, which correlated with serum IgG4 levels. The expression of BAFF-R and CD40 on B cells was significantly lower in IgG4-RD patients compared with those in pSS patients and HC. Unlike HC, Breg cells from pSS patients lacked suppressive functions.

Conclusions: B cells in patients with IgG4-RD and pSS display a variety of abnormalities, including disturbed B cell subpopulations, abnormal expression of key signaling molecules, co-stimulatory molecules, and inflammatory cytokines. In addition, a significantly increased B cell subset, CD19 + CD24-CD38(hi) B cells, may play an important role in the pathogenesis of IgG4-RD.

Citing Articles

The role of autoantibodies in bridging obesity, aging, and immunosenescence.

Valentino T, Chen N, Makhijani P, Khan S, Winer S, Revelo X Immun Ageing. 2024; 21(1):85.

PMID: 39616399 PMC: 11607830. DOI: 10.1186/s12979-024-00489-2.

Immune Cell Profiles of Patients with Sickle Cell Disease during Parvovirus B19-Induced Transient Red Cell Aplasia.

Allen E, Penkert R, Hankins J, Surman S, Van de Velde L, Cotton A Vaccines (Basel). 2024; 12(9).

PMID: 39340016 PMC: 11435734. DOI: 10.3390/vaccines12090984.

Bayesian-based analysis of the causality between 731 immune cells and erectile dysfunction: a two-sample, bidirectional, and multivariable Mendelian randomization study.

Chen J, Liu Y, Zhan P, Gao T, Zuo J, Li X Sex Med. 2024; 12(4):qfae062.

PMID: 39315306 PMC: 11416910. DOI: 10.1093/sexmed/qfae062.

Profiles of peripheral B cell subsets in a cohort of primary Sjögren's syndrome patients and their potential clinical significance.

Xing Y, Li B, Wei P, Hua H J Dent Sci. 2024; 19(3):1554-1563.

PMID: 39035330 PMC: 11259624. DOI: 10.1016/j.jds.2023.12.024.

Viral DNA in submandibular gland tissue with an inflammatory disorder.

Keski-Santti N, Waltimo E, Makitie A, Hagstrom J, Soderlund-Venermo M, Atula T J Oral Microbiol. 2024; 16(1):2345941.

PMID: 38711909 PMC: 11073405. DOI: 10.1080/20002297.2024.2345941.

References

Tanaka A, Moriyama M, Nakashima H, Miyake K, Hayashida J, Maehara T . Th2 and regulatory immune reactions contribute to IgG4 production and the initiation of Mikulicz disease. Arthritis Rheum. 2011; 64(1):254-63. DOI: 10.1002/art.33320. View

Majlessi L, Lo-Man R, Leclerc C . Regulatory B and T cells in infections. Microbes Infect. 2008; 10(9):1030-5. DOI: 10.1016/j.micinf.2008.07.017. View

Wilde B, Thewissen M, Damoiseaux J, Knippenberg S, Hilhorst M, van Paassen P . Regulatory B cells in ANCA-associated vasculitis. Ann Rheum Dis. 2013; 72(8):1416-9. DOI: 10.1136/annrheumdis-2012-202986. View

Carsetti R, Rosado M, Wardmann H . Peripheral development of B cells in mouse and man. Immunol Rev. 2004; 197:179-91. DOI: 10.1111/j.0105-2896.2004.0109.x. View

Li X, Zhong H, Bao W, Boulad N, Evangelista J, Haider M . Defective regulatory B-cell compartment in patients with immune thrombocytopenia. Blood. 2012; 120(16):3318-25. PMC: 3476542. DOI: 10.1182/blood-2012-05-432575. View

Karimi M, Pourfathollah A . CD40 and tolerance induction. Iran J Allergy Asthma Immunol. 2012; 11(1):1-13. DOI: 011.01/ijaai.113. View

Lemoine S, Morva A, Youinou P, Jamin C . Regulatory B cells in autoimmune diseases: how do they work?. Ann N Y Acad Sci. 2009; 1173:260-7. DOI: 10.1111/j.1749-6632.2009.04651.x. View

Sellam J, Miceli-Richard C, Gottenberg J, Ittah M, Lavie F, Lacabaratz C . Decreased B cell activating factor receptor expression on peripheral lymphocytes associated with increased disease activity in primary Sjögren's syndrome and systemic lupus erythematosus. Ann Rheum Dis. 2006; 66(6):790-7. PMC: 1954659. DOI: 10.1136/ard.2006.065656. View

Watanabe R, Ishiura N, Nakashima H, Kuwano Y, Okochi H, Tamaki K . Regulatory B cells (B10 cells) have a suppressive role in murine lupus: CD19 and B10 cell deficiency exacerbates systemic autoimmunity. J Immunol. 2010; 184(9):4801-9. PMC: 3734559. DOI: 10.4049/jimmunol.0902385. View

10.

Mauri C, Bosma A . Immune regulatory function of B cells. Annu Rev Immunol. 2012; 30:221-41. DOI: 10.1146/annurev-immunol-020711-074934. View

11.

Fairfax K, Mackay I, Mackay F . BAFF/BLyS inhibitors: A new prospect for treatment of systemic lupus erythematosus. IUBMB Life. 2012; 64(7):595-602. DOI: 10.1002/iub.1046. View

12.

Kuchroo V, Das M, Brown J, Ranger A, Zamvil S, Sobel R . B7-1 and B7-2 costimulatory molecules activate differentially the Th1/Th2 developmental pathways: application to autoimmune disease therapy. Cell. 1995; 80(5):707-18. DOI: 10.1016/0092-8674(95)90349-6. View

13.

Biragyn A, Lee-Chang C . A new paradigm for an old story: the role of regulatory B cells in cancer. Front Immunol. 2012; 3:206. PMC: 3401824. DOI: 10.3389/fimmu.2012.00206. View

14.

Blair P, Norena L, Flores-Borja F, Rawlings D, Isenberg D, Ehrenstein M . CD19(+)CD24(hi)CD38(hi) B cells exhibit regulatory capacity in healthy individuals but are functionally impaired in systemic Lupus Erythematosus patients. Immunity. 2010; 32(1):129-40. DOI: 10.1016/j.immuni.2009.11.009. View

15.

Umehara H, Okazaki K, Masaki Y, Kawano M, Yamamoto M, Saeki T . A novel clinical entity, IgG4-related disease (IgG4RD): general concept and details. Mod Rheumatol. 2011; 22(1):1-14. PMC: 3278618. DOI: 10.1007/s10165-011-0508-6. View

16.

Knippenberg S, Peelen E, Smolders J, Thewissen M, Menheere P, Cohen Tervaert J . Reduction in IL-10 producing B cells (Breg) in multiple sclerosis is accompanied by a reduced naïve/memory Breg ratio during a relapse but not in remission. J Neuroimmunol. 2011; 239(1-2):80-6. DOI: 10.1016/j.jneuroim.2011.08.019. View

17.

Mann M, Ray A, Basu S, Karp C, Dittel B . Pathogenic and regulatory roles for B cells in experimental autoimmune encephalomyelitis. Autoimmunity. 2012; 45(5):388-99. PMC: 3639139. DOI: 10.3109/08916934.2012.665523. View

18.

Mauri C . Regulation of immunity and autoimmunity by B cells. Curr Opin Immunol. 2010; 22(6):761-7. DOI: 10.1016/j.coi.2010.10.009. View

19.

Kanari H, Kagami S, Kashiwakuma D, Oya Y, Furuta S, Ikeda K . Role of Th2 cells in IgG4-related lacrimal gland enlargement. Int Arch Allergy Immunol. 2010; 152 Suppl 1:47-53. DOI: 10.1159/000312125. View

20.

Ebbo M, Daniel L, Pavic M, Seve P, Hamidou M, Andres E . IgG4-related systemic disease: features and treatment response in a French cohort: results of a multicenter registry. Medicine (Baltimore). 2011; 91(1):49-56. DOI: 10.1097/MD.0b013e3182433d77. View