The Contribution of B Cells in Autoimmune Liver Diseases

Abstract

Autoreactive B cells can promote autoimmunity through antigen presentation to autoreactive T cells, production of autoantibodies, generation of cytokines promoting T cell activation and differentiation, and inhibition of regulatory T cells and B cells. Here, the authors highlight studies pertaining to B cell mechanisms associated with disease pathogenesis and outcomes in autoimmune hepatitis and the immune-mediated cholangiopathies (primary biliary cholangitis, primary sclerosing cholangitis, and biliary atresia). The vast majority of investigations focus on autoantibodies and future research endeavors should include deciphering the role of the B cell in T cell activation (through antigen presentation, cytokine/chemokine production, and inhibition of regulation). Targeting B cell mechanisms in the treatment of autoimmune liver diseases is also highlighted.

Antigen presentation, autoantibody production, and therapeutic targets in autoimmune liver disease

“…127 Autoreactive B lymphocytes In addition to their canonical immunoregulatory roles, such as antibody production, antigen presentation and the induction of T cells, autoreactive B cells can trigger the secretion of proinflammatory cytokines and T cell activation, leading to the differentiation of pathogenic effector T cells. 6 Moreover, autoreactive B cells can inhibit Treg and regulatory B cells (Bregs or B10 cells in mice). 6 Furthermore, antibody-secreting plasma cells are abundant in inflammatory infiltrates in patients with AIH.…”

“…167 Targeting B cells in autoimmune liver injury The pathogenic role of B cells in autoimmune diseases has been established in diabetes type 1, SLE, and arthritis. 6 By presenting self-antigens, producing autoantibodies and secreting IL-21, B cells can contribute to the induction and maintenance of autoimmune diseases. Consequently, targeting B cells may provide novel strategies in the treatment of autoimmune diseases and in the liver.…”

Immunopathogenesis of Autoimmune Hepatitis†

“…The role of B cells in promoting AIH has historically been underemphasized in the context of this T cell–mediated disease. However, B cells play an important role in AIH both by generating autoantibodies and by inducing T cell responses through antigen presentation and cytokine production . Autoantibodies in AIH are clinically useful as diagnostic biomarkers for categorizing disease subtypes.…”

“…However, B cells play an important role in AIH both by generating autoantibodies and by inducing T cell responses through antigen presentation and cytokine production. 9 Autoantibodies in AIH are clinically useful as diagnostic biomarkers for categorizing disease subtypes. In addition, type 2 AIH, which has a specific autoantibody (anti-LKM [Liver-Kidney Microsomal antibody]), is characterized by an immunodominant epitope on the hepatocyte membrane (cytochrome P450 2D6 [CYP2D6]) that is the actual disease-specific autoantigen and plays a direct pathogenic role.…”

The challenges of primary biliary cholangitis: What is new and what needs to be done

“…Increasing awareness coupled with the aging of the population may lead to higher numbers of elderly patients diagnosed with PBC who have mild disease, whereas the number of younger patients with more aggressive, clinically apparent disease remains stable over time (14). AMA are increasingly tested, substantially contributing to the diagnosis of PBC at early stages and remains the immunological platform used to understand loss of tolerance (29)(30)(31).…”