Regulatory B cells in human inflammatory and autoimmune diseases: from mouse models to clinical research

Abstract

B cells have been generally considered to be positive regulators of immune responses because of their ability to produce antigen-specific antibodies and to activate T cells through antigen presentation. Impairment of B cell development and function may cause inflammatory and autoimmune diseases. Recently, specific B cell subsets that can negatively regulate immune responses have been described in mouse models of a wide variety of inflammatory and autoimmune diseases. The concept of those B cells, termed regulatory B cells, is now recognized as important in the murine immune system. Among several regulatory B cell subsets, IL-10-producing regulatory B cells are the most widely investigated. On the basis of discoveries from studies of such mice, human regulatory B cells that produce IL-10 in most cases are becoming an active area of research. There have been emerging data suggesting the importance of human regulatory B cells in various diseases. Revealing the immune regulation mechanisms of human regulatory B cells in human inflammatory and autoimmune diseases could lead to the development of novel B cell targeted therapies. This review highlights the current knowledge on regulatory B cells, mainly IL-10-producing regulatory B cells, in animal models of inflammatory and autoimmune diseases and in clinical research using human samples.

Regulatory B cells promote graft-versus-host disease prevention and maintain graft-versus-leukemia activity following allogeneic bone marrow transplantation

“…10,11 Regulatory B cells (Bregs) are a newly described subset of B cells that appears to play important roles in autoimmunity. [12][13][14][15][16][17] Human Bregs were enriched in both transitional (CD24 …”

Anti-B-Cell Therapies in Autoimmune Neurological Diseases: Rationale and Efficacy Trials

“…As already alluded to, the modern view for the role of B cells in the immune response implicates them in antigen presentation, antibody secretion, and optimal regulation of T-cell activation [37]. In autoimmunity, probably the most important effector action of B cells is the production of autoantibodies by plasma cells that have evaded the self-tolerance check points [38].…”

Human B Regulatory Cells: The New Players in Autoimmune Disease

“…Among these, several regulatory B-cell subsets (collectively designated as Bregs) are now being recognized and have been recently characterized, particularly those present in humans (Table 1), although their origins and relations to each other are not completely clear [1][2][3] .…”

“…Functional and numerical alterations in Bregs have been reported in several autoimmune diseases where inverse correlations between Bregs activity and disease severity are present 3 .…”

“…A suppressive B-cell subset was first identified in helminth-infected patients with multiple sclerosis (MS) who displayed an increased frequency of CD19 In systemic lupus erythematosus (SLE) patients, the inability of immature CD19 + CD24 hi CD38 hi B-cells to differentiate into Bregs has been detected together with an impaired IL-10-producing ability upon CD40 activation, affecting in this way, any Th1 response-suppression effect 2,3 . SLE is characterized by an IFN-α-induced signature that impacts in immature B-cell differentiation.…”