Molecular mechanisms controlling age‐associated B cells in autoimmunity

Age‐associated B cells (ABCs) have emerged as critical components of immune responses. Their inappropriate expansion and differentiation have increasingly been linked to the pathogenesis of autoimmune disorders, aging‐associated diseases, and infections. ABCs exhibit a distinctive phenotype and, in...

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Bibliographic Details
Published in:Immunological reviews 2022-05, Vol.307 (1), p.79-100
Main Authors: Phalke, Swati, Rivera‐Correa, Juan, Jenkins, Daniel, Flores Castro, Danny, Giannopoulou, Evgenia, Pernis, Alessandra B.
Format: Article
Language:English
Subjects:
age‐associated B cells
Aging
Antibodies
Antigens
Autoimmune diseases
Autoimmune Diseases - therapy
Autoimmunity
B-Lymphocytes
CD11c Antigen
CD11c+T‐bet
Control systems
Critical components
Def6
Female
Heterogeneity
Humans
Inflammation
IRF
IRF5
IRF8
Lymphocytes B
Male
Markers
Molecular machines
Molecular modelling
Pathogenesis
Phenotypes
Progeny
SWAP‐70
SWEF
T‐bet
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Summary:Age‐associated B cells (ABCs) have emerged as critical components of immune responses. Their inappropriate expansion and differentiation have increasingly been linked to the pathogenesis of autoimmune disorders, aging‐associated diseases, and infections. ABCs exhibit a distinctive phenotype and, in addition to classical B cell markers, often express the transcription factor T‐bet and myeloid markers like CD11c; hence, these cells are also commonly known as CD11c+T‐bet+ B cells. Formation of ABCs is promoted by distinctive combinations of innate and adaptive signals. In addition to producing antibodies, these cells display antigen‐presenting and proinflammatory capabilities. It is becoming increasingly appreciated that the ABC compartment exhibits a high degree of heterogeneity, plasticity, and sex‐specific regulation and that ABCs can differentiate into effector progeny via several routes particularly in autoimmune settings. In this review, we will discuss the initial insights that have been obtained on the molecular machinery that controls ABCs and we will highlight some of the unique aspects of this control system that may enable ABCs to fulfill their distinctive role in immune responses. Given the expanding array of autoimmune disorders and pathophysiological settings in which ABCs are being implicated, a deeper understanding of this machinery could have important and broad therapeutic implications for the successful, albeit daunting, task of targeting these cells.
ISSN:0105-2896
1600-065X
DOI:10.1111/imr.13068