Regulatory B Cells and Its Role in Central Nervous System Inflammatory Demyelinating Diseases

Abstract

Regulatory B (Breg) cells represent a population of suppressor B cells that participate in immunomodulatory processes and inhibition of excessive inflammation. The regulatory function of Breg cells have been demonstrated in mice and human with inflammatory diseases, cancer, after transplantation, and particularly in autoinflammatory disorders. In order to suppress inflammation, Breg cells produce anti-inflammatory mediators, induce death ligand-mediated apoptosis, and regulate many kinds of immune cells such as suppressing the proliferation and differentiation of effector T cell and increasing the number of regulatory T cells. Central nervous system Inflammatory demyelinating diseases (CNS IDDs) are a heterogeneous group of disorders, which occur against the background of an acute or chronic inflammatory process. With the advent of monoclonal antibodies directed against B cells, breakthroughs have been made in the treatment of CNS IDDs. Therefore, the number and function of B cells in IDDs have attracted attention. Meanwhile, increasing number of studies have confirmed that Breg cells play a role in alleviating autoimmune diseases, and treatment with Breg cells has also been proposed as a new therapeutic direction. In this review, we focus on the understanding of the development and function of Breg cells and on the diversification of Breg cells in CNS IDDs.

B Cell Orchestration of Anti-tumor Immune Responses: A Matter of Cell Localization and Communication

“…Recently, a solution to this problem was proposed employing Toll-like receptor ligands, together with high dimensional data-analysis ( Chaye et al, 2021 ). The available data suggest that Breg cells can arise at various stages during B cell development and differentiation in response to various cues, including cytokines (e.g., IL-35, IL-21, IL-1β, and IL-6) ( Yoshizaki et al, 2012 ; Rosser et al, 2014 ; Wang et al, 2014 ; Dambuza et al, 2017 ), large amounts of calcium influx ( Matsumoto et al, 2011 ; Matsumoto and Baba, 2013 ) and activation of surface molecules such as TLRs, CD40 and BCRs ( Fillatreau et al, 2002 ; Yoshizaki et al, 2012 ; Rosser et al, 2014 ; Menon et al, 2016 ; Ran et al, 2020 ).…”

Elevated Circulating IL-10 Producing Breg, but Not Regulatory B Cell Levels, Restrain Antibody-Mediated Rejection After Kidney Transplantation

“…Accumulating evidence suggests that under inflammatory circumstances, B cells can differentiate into antibody-secreting plasmablasts and regulatory B cells (Bregs), which are a special B cell subset that secretes immunosuppressive cytokines, particularly interleukin (IL)-10. ( 1 , 5 – 7 ). Thus, plasmablasts produce alloantibodies, resulting in AMR, while Bregs exhibit immunoregulatory functions and help induce immune homeostasis.…”

Aspects of the Tumor Microenvironment Involved in Immune Resistance and Drug Resistance

“…On the other hand, B cells have been shown to differentiate into another tumor-associated cell. An IL-10-secreting B cell named Breg ( 147 ) promoted metastasis of breast cancer ( 148 ) and it has been shown to be implicated in inflammation-induced squamous cell carcinoma through the secretion of TNF-α in animal models ( 149 ). It should be noted that this B cell was non-infiltrating – that is, present only in the surrounding tissue – thus further studies are warranted to determine if they behave the same way in human cancers.…”