Regulatory B cells: TIM‐1, transplant tolerance, and rejection

Abstract

Regulatory B cells (Bregs) ameliorate autoimmune disease and prevent allograft rejection. Conversely, they hinder effective clearance of pathogens and malignancies. Breg activity is mainly attributed to IL‐10 expression, but also utilizes additional regulatory mechanisms such as TGF‐β, FasL, IL‐35, and TIGIT. Although Bregs are present in various subsets defined by phenotypic markers (including canonical B cell subsets), our understanding of Bregs has been limited by the lack of a broadly inclusive and specific phenotypic or transcriptional marker. TIM‐1, a broad marker for Bregs first identified in transplant models, plays a major role in Breg maintenance and induction. Here, we expand on the role of TIM‐1+ Bregs in immune tolerance and propose TIM‐1 as a unifying marker for Bregs that utilize various inhibitory mechanisms in addition to IL‐10. Further, this review provides an in‐depth assessment of our understanding of Bregs in transplantation as elucidated in murine models and clinical studies. These studies highlight the major contribution of Bregs in preventing allograft rejection, and their ability to serve as highly predictive biomarkers for clinical transplant outcomes.

TIM-1+ B Cells are more Efficient IL-10 Producers in Liver Fibrosis Caused by Alveolar Echinococcosis

“…In recent years, more and more researchers have noticed a new subset of B cells that secrete IL-10 more e ciently, TIM-1 + B cells. Examination of TIM-1 + B cells revealed a 20-to 25-fold enrichment for IL-10 compared to TIM-1 − B cells [9]. TIM-1 binds to phosphatidylserine, which is ipped to the outer lea et of apoptotic cell membranes, conveying phagocytosis by macrophages and IL-10 expression by B cells.…”

“…TIM-1 binds to phosphatidylserine, which is ipped to the outer lea et of apoptotic cell membranes, conveying phagocytosis by macrophages and IL-10 expression by B cells. Therefore, some researchers suggest that TIM-1 is one of the markers for the identi cation of Breg subset [9,22]. Studies have shown that mouse TIM-1 + B cells can suppress Th1 response in vivo and promote Th2 and Treg responses in an allograft transplantation setting [23].…”

“…Regulatory B cells (Bregs) are a special subset of B cells that have immune regulation or immunosuppressive functions, and play an important role in peripheral immune tolerance. The activity of Breg is mainly attributable to the expression of IL-10, but also uses additional regulatory mechanisms such as TGF-β, FasL, IL-35 and TIGIT [8,9]. T cells immunoglobulin domain and mucin domain protein-1 (TIM-1) is a transmembrane glycoprotein that has been identi ed as a member of the TIM family of genes that regulate immune response.…”

B Home or You Are In Trouble: B Cell Integrin—Mediated Recruitment Attenuates Skin Inflammation

“…Deciphering B cell function within tissues is complicated by the lack of transcriptionally encoded distinction between regulatory and pathogenic cells. Although B cells can be divided into B1 (innate-like) and B2 (adaptive) subsets, both populations have the capacity to give rise to IL-10eproducing cells (Cherukuri et al, 2021). Furthermore, no driving transcription factor akin to Foxp3 for regulatory T cells has been identified.…”

“…Furthermore, no driving transcription factor akin to Foxp3 for regulatory T cells has been identified. Instead, Bregs likely arise owing to contextually dependent differentiation and recruitment signals (Cherukuri et al, 2021;Rosser and Mauri, 2015).…”