Age-associated B cells indicate disease activity in rheumatoid arthritis

Bao, Weijia; Xie, Maosheng; Ye, Yujin

doi:10.1016/j.cellimm.2022.104533

Cited by 12 publications

(10 citation statements)

References 43 publications

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“…In contrast to a recent study [42], we did not find that the frequency of ABCs was increased in either eRA or estRA compared to age‐matched HC. This discrepancy may be explained by the difference in the definition of ABCs: We defined ABCs as CD21 − CD11c + B cells, whereas Bao et al defined them as T‐bet + CD11c + B cells.…”

Section: Discussioncontrasting

confidence: 99%

Characterization of age‐associated B cells in early drug‐naïve rheumatoid arthritis patients

et al. 2022

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Age-associated B cells (ABCs) are an immune cell subset linked to autoimmunity, infection and ageing, and whose pathophysiological importance was recently highlighted using single cell synovial tissue profiling. To elucidate their pathophysiological relevance, peripheral blood (PB) ABCs from early rheumatoid arthritis (eRA) patients naïve to disease-modifying anti-rheumatic drugs (DMARDs) were compared with their synovial fluid (SF) counterparts, and to PB ABCs from psoriatic arthritis patients and healthy controls. PB and SF B-cell subsets were phenotyped by multi-parameter flow cytometry, sorted and subjected to gene expression profiling (NanoString nCounter ® Immunology V2 Panel) and functional characterization (stimulated cytokine measurements by immunoassay). PB ABCs of eRA patients, which are transcriptionally distinct from those of control cohorts, express chemokine receptors and adhesion molecules, such as CXCR3, that favour homing to inflammatory sites over lymphoid tissue. These cells are an activated, classswitched B-cell subset expressing high levels of HLA-DR, co-stimulatory molecules and T-bet. Their secretion profile includes IL-12p70 and IL-23 but low levels of IL-10. High surface expression of FcRL family members, including FcRL3, furthermore suggests a role for these cells in autoimmunity. Finally, and unlike in the periphery where they are rare, ABCs are the predominant B-cell subsets in SF. These observations indicate the predilection of ABCs for inflammatory tissue in RA, where their propensity for antigen presentation and pro-inflammatory phenotype may support autoimmune pathology. Their potential as a therapeutic target therefore warrants further study.

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Section: Discussioncontrasting

confidence: 99%

Characterization of age‐associated B cells in early drug‐naïve rheumatoid arthritis patients

et al. 2022

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“…Actually, increased frequency of CD27 - IgM - IgD - CD21 - ABC-like B cells was observed in patients with seropositive RA compared with healthy individuals ( 72 ). Our group recently found that ABCs were expanded both in collagen-induced arthritis mice and in the circulation of RA patients with more severe symptom ( 30 ).Similarly, another group also demonstrated that circulating ABCs were increased in RA patients with higher disease activity and decreased in those with good treatment responses ( 73 ).…”

Section: Abcs In Rheumatoid Arthritismentioning

confidence: 92%

Age/autoimmunity-associated B cells in inflammatory arthritis: An emerging therapeutic target

Cai

Qin

et al. 2023

Front. Immunol.

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Age/autoimmunity-associated B cells (ABCs) are a novel B cell subpopulation with a unique transcriptional signature and cell surface phenotype. They are not sensitive to BCR but rely on TLR7 or TLR9 in the context of T cell-derived cytokines for the differentiation. It has been established that aberrant expansion of ABCs is linked to the pathogenesis of systemic autoimmune diseases such as systemic lupus erythematosus. Recently, we and other groups have shown that increased ABCs is associated with rheumatoid arthritis (RA) disease activity and have demonstrated their pathogenic role in RA, indicating that targeting specific B cell subsets is a promising strategy for the treatment of inflammatory arthritis. In this review, we summarize the current knowledge of ABCs, focusing on their emerging role in the pathogenesis of inflammatory arthritis. A deep understanding of the biology of ABCs in the context of inflammatory settings in vivo will ultimately contribute to the development of novel targeted therapies for the treatment of inflammatory arthritis.

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“…In ACPA + /RF + patients with established RA, CD21–/lowCD27–IgD–FcRL4– MBCs are expanded, and the frequencies of these cells correlate with joint destruction [ 25 ]. In another study, CD11c+Tbet+ B cells (of unknown CD21 and CD27 status) were found to associate with inflammation and disease activity (disease activity score 28 joints (DAS28)) [ 64 ]. Moreover, the frequency of CD21–/low that are CD27+ was increased in female RA patients and was found to correlate with age [ 11 ].…”

Section: Autoimmune Diseasesmentioning

confidence: 99%

A close-up on the expanding landscape of CD21–/low B cells in humans

Gjertsson

McGrath

Grimstad

et al. 2022

Clinical and Experimental Immunology

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Memory B cells (MBCs) are an essential part of our immunological memory. They respond fast upon re-encountering pathogens and can differentiate into plasma cells that secrete protective antibodies. The focus of this review is on MBCs that lack, or express low levels of, CD21, hereafter referred to as CD21-/low. These cells are expanded in peripheral blood with age and during chronic inflammatory conditions such as viral infections, malaria, common variable immunodeficiency, and autoimmune diseases. CD21-/low MBCs have gained significant attention; they produce disease-specific antibodies/autoantibodies, and associate with key disease manifestations in some conditions. However, these cells can be divided into subsets based on classical B-cell and other markers, e.g., CD11c, FcRL4 and Tbet that, over the years, have become hallmarks to identify these cells. This has resulted in different names including age-associated, autoimmune-associated, atypical, tissue-like, tissue-resident, tissue-restricted, exhausted or simply CD21-/low B cells. It is however unclear whether the expanded ‘CD21-/low’ cells in one condition are equivalent to those in another, whether they express an identical gene signature and whether they have a similar function. Here, we will discuss these issues with the goal to understand whether the CD21-/low B cells are comparable in the different conditions.

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Age-associated B cells indicate disease activity in rheumatoid arthritis

Cited by 12 publications

References 43 publications

Characterization of age‐associated B cells in early drug‐naïve rheumatoid arthritis patients

Characterization of age‐associated B cells in early drug‐naïve rheumatoid arthritis patients

Age/autoimmunity-associated B cells in inflammatory arthritis: An emerging therapeutic target

A close-up on the expanding landscape of CD21–/low B cells in humans

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