Functional variants of the B cell gene, B cell scaffold protein with ankyrin repeats 1 (BANK1) contribute to rheumatoid arthritis (RA) susceptibility, but their influences on B cell responses are unclear. Moreover, the function of induced T regulatory cells (iTregs) in the inflammatory milieu in a collagen-induced arthritis (CIA) model is unknown. This study was performed to investigate the roles of BANK1 in CIA and the interaction between B cells and iTregs.
The changes in BANK1 mRNA and protein levels and their correlation with disease severity in CIA were determined. Next, the antigen-presenting function and autoantibody production in B cells were evaluated by co-culture with effector T cells and iTregs, respectively, both in vitro and in vivo. Then, the mechanisms underlying these interactions were studied by adding neutralizing antibodies or transwell inserts and by adoptive transfer to B-cell-depleted CIA mice.
The BANK1 level decreased in the peripheral blood, spleen and lymph nodes of CIA mice, particularly during the acute stage of arthritis, and exhibited negative correlation with disease severity and autoantibody production. B cell responses were enhanced by this decrease. B cells from CIA mice (CIA-B cells) promoted iTreg differentiation, proliferation and cytotoxic T lymphocyte-associated protein-4 (CTLA-4) expression. Meanwhile, BANK1 expression in CIA-B cells increased after co-culture with iTregs, limiting B cell responses. All these interactions depended on cell contact with CTLA-4-overexpressing iTregs but were independent of CTLA-4 cytokine.
Decreased BANK1 expression promotes B cell responses, resulting in an increased antigen presentation ability and autoantibody production that subsequently influences the communication between B cells and iTregs through a cell-contact-dependent and CTLA-4- cytokine-independent mechanism in CIA mice.
Angelotti F, Parma A, Cafaro G, Capecchi R, Alunno A, Puxeddu I. One year in review 2017: pathogenesis of rheumatoid arthritis. Clin Exp Rheumatol. 2017;35(3):368–78. PubMed
Cohen SB, Emery P, Greenwald MW, et al. Rituximab for rheumatoid arthritis refractory to anti-tumor necrosis factor therapy: Results of a multicenter, randomized, double-blind, placebo-controlled, phase III trial evaluating primary efficacy and safety at twenty-four weeks. Arthritis Rheum. 2006;54:2793–806. CrossRefPubMed
Yuichi A, Tetsuo Y, Okada T, et al. BANK Negatively Regulates Akt activation and subsequent B cell responses. Immunity. 2006;24:259–68. CrossRef
Kong N, Wu Z, Jiang L, et al. The association of BANKl single nucleotide polymorphisms with rheumatoid arthritis in Chinese Han population. Chin J Rheumatol. 2012;16(2):82–6.
Järvinen TM, Hellquist A, Zucchelli M, et al. Replication of GWAS-identified systemic lupus erythematosus susceptibility genes affirms B-cell receptor pathway signaling and strengthens the role of IRF5 in disease susceptibility in a Northern European population. Rheumatology (Oxford). 2012;51(1):87–92. CrossRef
Cantaert T, Yeremenko NG, Teitsma CA, et al. Altered BANK1 expression is not associated with humoral autoimmunity in chronic joint inflammation. Rheumatology (Oxford). 2013;52(2):252–60. CrossRef
Kenneth M. Janeway's immunobiology 8th edition. New York, NY: Garland Science; 2012. ISBN 9780815342434.
Serreze DV, Fleming SA, Chapman HD, et al. B lymphocytes are critical antigen-presenting cells for the initiation of T cell-mediated autoimmune diabetes in nonobese diabetic mice. J Immunol. 1998;161:3912–8. PubMed
Kong N, Lan Q, Chen M, et al. Antigen-specific transforming growth factor β-induced Treg cells, but not natural Treg cells, ameliorate autoimmune arthritis in mice by shifting the Th17/Treg cell balance from Th17 predominance to Treg cell predominance. Arthritis Rheum. 2012;64(8):2548–58. CrossRefPubMedPubMedCentral
Isenberg DA. Review by Hui-Yuen et al. Targeted B-cell therapies in the treatment of adult and paediatric systemic lupus erythematosus. Lupus. 2017;26(8):900.
Chikuma S. CTLA-4, an essential immune-checkpoint for T-cell activation. Curr Top Microbiol Immunol. 2017;410:99–126. PubMed
- BANK1 alters B cell responses and influences the interactions between B cells and induced T regulatory cells in mice with collagen-induced arthritis
- BioMed Central
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