BANK1 alters B cell responses and influences the interactions between B cells and induced T regulatory cells in mice with collagen-induced arthritis

Abstract

BackgroundFunctional 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.MethodsThe 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.ResultsThe 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.ConclusionDecreased 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.

Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland

“…Utilizing classical markers B-lymphocyte antigen Cluster of Differentiation 19 (Cd19) and Ms4a1 [76,77], our analyses identified two clusters with B-lymphoid lineage identity (mNEC1 and mNEC6). They both showed the expression of immunoglobulin-like genes Immunoglobulin Kappa Constant (Igkc), Immunoglobulin Heavy Constant Mu (Ighm), Immunoglobulin Heavy Constant Delta (Ighd) and additional B-cell markers, such as Cd79a [78], Cluster of Differentiation 83 (Cd83) [79], B Cell Scaffold Protein with Ankyrin Repeats 1 (Bank1) [80], and Paired Box 5 (Pax5) [81] (Fig. 4C, and Supplementary Fig.…”

B Cell Immunophenotyping and Expression Analysis of B Cell Specific Molecules of Patients with Benign Multiple Sclerosis

“…Verbal response test results were found to be high in cases with no expression level change between benign and non-BMS cases, and low levels of expression of BANK1 gene (11) which had an effect on B lymphocyte proliferation. The association of this factor with B cell functions is well known, but there are no studies showing its association with MS.…”

“…In this case, plasmablast and plasma cell production in lymphoid tissue is increased or memory cells in brain tissue start to produce pathogenic antibodies (6). Therefore, the most common B cell subtype found in MS plaques is a long-lasting plasma cell (11,15). The fact that monoclonal antibody-based treatment methods targeting B cells are effective in stopping the progression of the disease suggested that B cells also play a role in the development of disability (8,9).…”

Chronic disturbance in the thalamus following cranial irradiation to the developing mouse brain

“…For example, Sfrp4 , known to inhibit the Wnt pathway that controls cell proliferation, differentiation and migration, was downregulated following CIR 25 . The gene expression data do however also indicate that there is an ongoing injury ( Bank1, Il1a , and Pdgfra ) 17–19 (Fig. 5), and all genes related to ECM were downregulated (Fig.…”

“…The thalamic astrocytes are presumably set to a healing state, with activated clearance mechanisms and lower levels of inflammation, as indicated by increased levels of Nov , Gpnmb, Ces2f and Ephx1 13–16 . However, some genes ( Bank1, Il1a , and Pdgfra ) indicate that there is still an ongoing injury present as long as 4 months following CIR 17–19 .…”