Suppressive functions of activated B cells in autoimmune diseases reveal the dual roles of Toll‐like receptors in immunity

Abstract

B lymphocytes contribute to immunity through production of antibodies, antigen presentation to T cells, and secretion of cytokines. B cells are generally considered in autoimmune diseases as drivers of pathogenesis. This view is certainly justified, given the successful utilization of the B cell-depleting reagent rituximab in patients with rheumatoid arthritis or other autoimmune pathologies. In a number of cases, however, the depletion of B cells led to an exacerbation of symptoms in patients with autoimmune disorders. In a similar manner, mice lacking B cells can develop an aggravated course of disease in several autoimmune models. These paradoxical observations are now explained by the concept that activated B cells can suppress immune responses through the production of cytokines, especially interleukin-10. Here, we review the stimulatory signals that induce interleukin-10 secretion and suppressive functions in B cells and the phenotype of the B cells with such characteristics. Finally, we formulate a model explaining how this process of immune regulation by activated B cells can confer advantageous properties to the immune system in its combat with pathogens. Altogether, this review proposes that B-cell-mediated regulation is a fundamental property of the immune system, with features of great interest for the development of new cell-based therapies for autoimmune diseases.

Probiotics Applications in Autoimmune Diseases

“…As the human gut contains such large volumes of beneficial bacteria, they constantly trigger the TLRs. This leads to an eventual attenuation in the TLR response [82][83][84], (see Figure 2). …”

Regulatory B Cells - Implications in Autoimmune and Allergic Disorders

“…Some regulatory B cell populations have also been shown to be induced in diverse disease settings and in response to many different exogenous and endogenous stimuli. Toll-like receptor (TLR) signalling via TLR-2, 4 and 9 as well as B cell receptor (BCR) signalling and co-stimulation mediated by CD40, CD80/CD86 or B-cell activating factor (BAFF) has been demonstrated to induce B cells with suppressive activity (Fillatreau, Sweenie et al 2002;Mauri, Gray et al 2003;Blair, Chavez-Rueda et al 2009;Kala, Rhodes et al 2010;Lampropoulou, Calderon-Gomez et al 2010;Yang, Sun et al 2010 (Yanaba, Bouaziz et al 2008). The human equivalent to mouse B10 cells has been identified recently as a small population within peripheral blood CD24 hi CD27 + B cells (Iwata, Matsushita et al 2011).…”

B Lymphocytes Treated In Vitro with Antigen Coupled to Cholera Toxin B Subunit Induce Antigen-Specific Foxp3+ Regulatory T Cells and Protect against Experimental Autoimmune Encephalomyelitis

“…Recently, B lymphocytes have attracted growing attention as cells that may influence the development and regulation of not only autoantibody-associated, but also T cell-mediated, autoimmune disorders (1,2). Clinical studies have shown that treatment with Rituximab, a mouse-human chimeric anti-CD20 Ab, which effectively depletes naive and memory B cells from peripheral blood (3,4), is beneficial in many patients with rheumatoid arthritis (5,6), multiple sclerosis (7,8), and type 1 diabetes (9).…”

“…However, in some patients with these diseases (10,11), and in most patients with ulcerative colitis (12), treatment with Rituximab has led to an exacerbation of symptoms. Likewise, in mice, the depletion of B cells may lead to either amelioration or aggravation of autoimmune manifestations, and in several autoimmune disease models, a congenital lack of B cells is associated with an aggravated course of disease (1,2,6,8,9,(11)(12)(13)(14)(15). Consequently, it appears that similar to T cells, B cells can have dual functions in autoimmune diseases by both contributing to and suppressing disease development or progression.…”

“…Consequently, it appears that similar to T cells, B cells can have dual functions in autoimmune diseases by both contributing to and suppressing disease development or progression. Indeed, recent studies have confirmed that under some conditions, activated B cells can suppress effector T (Teff) cell responses through providing signals, including the production of IL-10 and TGF-b, that facilitate tolerance, and the development and expansion of Foxp3 + Treg and/or Tr1 cells (1,2). Several regulatory B (Breg) cell subsets have been described, most of which appear to have IL-10 production as regulatory mechanism (14)(15)(16)(17).…”