Regulatorische B-Zellen – immunpathologisches und prognostisches Potenzial beim Menschen

Zusammenfassung

Regulatorische B-Zellen (Bregs) stellen eine heterogene Gruppe von B-Zellen dar, welche in der Lage sind, inflammatorische Immunantworten zu unterdrücken. Bregs tragen damit zur Aufrechterhaltung von Toleranz und zur Immunhomöostase bei, indem sie laufende Immunreaktionen räumlich und zeitlich begrenzen. Die herausragende Rolle von Bregs bei der Eindämmung pathologisch überschießender Entzündungsreaktionen, mit der sowohl Allergien, Autoimmunerkrankungen und Transplantatabstoßungen, aber auch Infektionen, Neoplasien und Stoffwechselerkrankungen einhergehen können, wurde in einer Vielzahl von Tiermodellen nachgewiesen. Die ersten Studien zu Bregs identifizierten IL-10 als funktionelles Schlüsselmolekül, weshalb die murine IL-10-produzierende B10-Zelle noch immer als Prototyp für Bregs gilt und IL-10 bei der Suche nach humanen Äquivalenten für Bregs lange im Vordergrund stand. In den letzten 2 Jahrzehnten wurde jedoch eine ganze Reihe weiterer Moleküle entdeckt, die – teilweise auch ausschließlich in humanen Bregs – zu ihrer immunsuppressiven Funktion beitragen können. Zu diesem erweiterten Arsenal gehören zum einen weitere entzündungshemmende Zytokine wie IL-35 und TGF-β, aber auch Enzyme wie Granzym B, CD39/CD73 und IDO, sowie Zelloberflächenproteine wie CD1d, PD-L1 und CD25. Ziel des vorliegenden Übersichtsartikels soll es sein, die mutmaßliche Rolle von Bregs insbesondere bei unterschiedlichen Humanpathologien zu beleuchten und dabei ihre potenzielle therapeutische und prognostische Relevanz hervorzuheben.

Abstract

Regulatory B cells (Bregs) represent a heterogeneous group of B cells capable of suppressing inflammatory immune responses. Bregs thus contribute to the maintenance of tolerance and immune homeostasis by spatially and temporally limiting ongoing immune responses. The prominent role of Bregs in curbing pathological excessive inflammatory responses, which can be associated with allergies, autoimmune diseases, and graft rejections, but also with infections, neoplasms, and metabolic diseases, has been demonstrated in a vast variety of animal models. The first studies on Bregs identified IL-10 as a key functional molecule, which is why the murine IL-10-producing B10 cell is still considered the prototype for Bregs, and IL-10 was also for a long time in focus of the search for human equivalents for Bregs. However, in the last 2 decades, a whole range of further molecules have been discovered that may contribute to their immunosuppressive function, some of them exclusively in human Bregs. This expanded arsenal includes, on the one hand, additional anti-inflammatory cytokines such as IL-35 and TGF-β, but also enzymes such as granzyme B, CD39/CD73, and IDO, as well as cell surface proteins including CD1d, PD-L1, and CD25. The aim of this review article is to highlight the putative role of Bregs particularly in different human pathologies, highlighting their potential therapeutic and prognostic relevance.

Schlüsselwörter

Regulatorische B-Zelle (Breg) - Interleukin 10 - GraB-Zelle - Granzym B - Immunsuppression

Key words

Regulatory B cell (Breg) - Interleukin 10 - GraB cell - granzyme B - immunosuppression

Publication History

Article published online:
17 August 2023

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