Data Availability StatementYes. 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. Results The Lender1 level decreased in the peripheral blood, spleen and lymph nodes of CIA mice, particularly during the acute stage of arthritis, and exhibited unfavorable 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, Lender1 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 impartial of CTLA-4 cytokine. Conclusion Decreased Lender1 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. Background Rheumatoid arthritis (RA) is an autoimmune disease characterized by progressive, destructive arthritis and ultimately causes joint dysfunction. Both T cells and B c-Fms-IN-9 cells play an important role in RA pathogenesis [1C4]. Autoantibodies against rheumatoid factor (RF) and cyclic peptide made up of citrulline (CCP) are the main adverse prognostic factors [5C7] of RA. Rituximab, a chimeric monoclonal IgG-1 antibody against the CD20 molecule expressed on B cells, is usually a well-known treatment for diseases with too many B cells, overactive B cells and dysfunctional B cells. This biological agent has been licensed for patients with RA who Rabbit Polyclonal to PAK5/6 are refractory to first-line treatment [8, 9] and has confirmed the effects of B cells on this disease. The B cell scaffold protein with ankyrin repeats 1 (Lender1) is expressed in B cells, but not T cells, and promotes tyrosine phosphorylation of the IP3 receptor to modulate B cell antigen receptor (BCR)-induced calcium mobilization [10]. Lender1 also weakens CD40-mediated Akt activation to prevent B cell hyperaction [11]. In some studies, functional variants of BANK1 are associated with autoimmune diseases such as systemic lupus erythematosus (SLE) and RA [12C15]. However, only a few studies have verified the roles of the BANK1 protein in autoimmune diseases and immune-associated diseases. Tineke Cantaert et al. explored the effects of alterations in BANK1 expression on humoral autoimmunity in arthritis but did not identify an important role [16]. Some scientists have noticed that higher BANK1 transcript levels help maintain stable immune tolerance in the absence of immunosuppression [17]. Based on these data, BANK1 may negatively affect immune-regulatory mechanisms in some diseases. B cells interact with T cells through both BCRs and some molecules expressed on T cells that function as ligands [18]. This requires c-Fms-IN-9 B cell antigen-presentation to T cells and serial interactions between receptor/ligand pairs belonging to CD28/B7 and cytokine superfamilies. They cooperate to induce optimum effector T cell activation and shut-down, to initiate regulatory T cell development and negative immune responses [19]. These interactions activate B cells to increase the expression of costimulatory factors and proliferation, subsequently promoting their differentiation into antibody-producing plasma cells [20]. B cells have also been shown to function as crucial antigen-presenting cells (APCs) that present certain antigens to initiate autoreactive T cells [21, 22] and are essential for self-reactive CD4+ T cell activation [23]. Meanwhile, self-reactive CD4+ T cells, which mainly react to B cells that express costimulatory molecules [24C26], are c-Fms-IN-9 induced to differentiate into T helper cells (Th, which are also known as CD4+ T cells) such as Th17 and Th2 cells, which can produce considerably greater levels of pro-inflammatory factors and promote inflammatory c-Fms-IN-9 disease progression. Any interruption of the interactions between B cells and T cells potentially contributes to the development of immune-deficient and autoimmune diseases [18]. Induced T regulatory cells (iTregs) exert excellent preventive and therapeutic effects on collagen-induced arthritis (CIA) and induce the production of additional suppressive cells after adoptive transfer in a CIA c-Fms-IN-9 model in vivo [27], but the mechanism involved requires further exploration. In addition to T cells, regulatory T cells are also.