CD39 and CD326 Are Bona Fide Markers of Murine and Human Plasma Cells and Identify a Bone Marrow Specific Plasma Cell Subpopulation in Lupus

Dang, Van Duc; Mohr, Elodie; Szelinski, Franziska; Le, Tuan Anh; Ritter, Jacob; Hinnenthal, Timo; Stefanski, Ana‐Luisa; Schrezenmeier, Eva; Ocvirk, Soeren; Hipfl, Christian; Hardt, Sebastian; Cheng, Qingyu; Hiepe, Falk; Löhning, Max; Dörner, Thomas; Lino, Andreia C.

doi:10.3389/fimmu.2022.873217

Cited by 10 publications

(9 citation statements)

References 66 publications

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“…And restoration of CD81 expression induced a G1 cycle arrest and apoptosis in gastric tumor (Yoo et al 2013 ). Furthermore, the expression of CD81 in B cells from SLE patients was down-regulated, and that could be correlated with abnormal activation of B cells (especially antibody secreting cells) and disease activity (especially at the active stage) (Henriques et al 2016 ; Abu-Zahab et al 2017 ; Dang et al 2022 ). It suggested that CD81 could be a potential indicator for the diagnosis of SLE.…”

Section: Introductionmentioning

confidence: 99%

Hydroxychloroquine induces apoptosis of myeloid-derived suppressor cells via up-regulation of CD81 contributing to alleviate lupus symptoms

Zhu

et al. 2022

Mol Med

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Background Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder that results from widespread immune complex deposition and secondary tissue injury. Hydroxychloroquine (HCQ) has been used clinically to treat SLE, while its exact mechanism has still remained elusive. Some studies have shown that myeloid-derived suppressor cells (MDSCs) play a vital role in the regulation of SLE. In this study, we aimed to explore the effects of HCQ on the apoptosis of MDSCs in lupus mice and its possible molecular regulatory mechanism. Methods We constructed the imiquimod (IMQ)-induced lupus model in mice. The proportion and apoptosis of MDSCs were measured by flow cytometry. CD81-overexpressed adeno-associated virus was intraperitoneally injected into the lupus mice. We also transfected the CD81 siRNA into bone marrow-derived MDSCs, and employed qRT-PCR and Western blotting to quantify the level of CD81. Results The results showed that HCQ ameliorated IMQ-induced lupus symptoms, and simultaneously inhibited the expansion of MDSCs. In particular, HCQ induced the apoptosis of MDSCs, and also up-regulated the expression level of CD81 in MDSCs, which might indicate the relationship between the expression level of CD81 and the apoptosis of MDSCs. CD81 was further confirmed to participate in the apoptosis of MDSCs and lupus disease progression by overexpressing CD81 in vivo. Molecular docking experiment further proved the targeting effect of HCQ on CD81. And then we interfered CD81 in bone marrow derived MDSCs in vitro, and it was revealed that HCQ rescued the decreased expression level of CD81 and relieved the immune imbalance of Th17/Treg cells. Conclusion In summary, HCQ promoted the apoptosis of MDSCs by up-regulating the expression level of CD81 in MDSCs, and ultimately alleviated lupus symptoms. Our results may assist scholars to develop further effective therapies for SLE.

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Section: Introductionmentioning

confidence: 99%

Hydroxychloroquine induces apoptosis of myeloid-derived suppressor cells via up-regulation of CD81 contributing to alleviate lupus symptoms

Zhu

et al. 2022

Mol Med

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“…Through the use of intravenous Ab labeling and by blocking CD154(CD40L) signals in young mice, we demonstrated that THY ASCs were most likely generated locally and were dependent on T cell-derived signals for their generation. However, recent examination of LAG-3 + ASCs in the BM, SPL and mesenteric lymph node (mLN) demonstrated that at least some ASC populations gain independence from T cells for their generation over the course of aging (Dang et al, 2022). So why would this transition not take place in the THY?…”

Section: Discussionmentioning

confidence: 99%

Thymus Antibody-Secreting Cells Represent a Tissue Specific Population That Possess an Activated Cellular Phenotype

Pioli

Lau

Pioli

2022

Preprint

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Antibody-secreting cells (ASCs) are key contributors to humoral immunity through immunoglobulin production and the potential to be long-lived. ASCs have been recently identified in the thymus (THY) which is of interest as autoreactive THY B cells regulate T cell tolerance. Here, we showed that the young female THY was skewed towards higher production of ASCs relative to males. However, these differences disappeared with age. Intravenous labeling combined with blockade of CD154(CD40L) suggested that THY ASCs were generated in situ in a T cell dependent fashion. Single cell RNA-sequencing revealed that THY ASCs possessed a transcriptional signature indicative of interferon signaling and activation. Flow cytometry confirmed that THY ASCs had increased levels of Toll-like receptor 7 as well as the activation markers CD69 and major histocompatibility class II. Overall, THY ASCs are a unique population that require further investigation to fully appreciate their biological significance.

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“…Therefore, most CD138 int FO B cells are not committed to plasma cells but maintain their B cell identity. Cell surface proteins in plasma cells were recently elucidated by investigating Blimp-1-expressing cells ( 53 ). Our data showed that CD138 int B cells did not express any of the plasma cell surface proteins mentioned in the article, except CD138.…”

Section: Discussionmentioning

confidence: 99%

Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

et al. 2022

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Autoreactive B cells are not entirely deleted, but some remain as immunocompetent or anergic B cells. Although the persistence of autoreactive B cells as anergic cells has been shown in transgenic mouse models with the expression of B cell receptor (BCR) reactive to engineered self-antigen, the characterization of naturally occurring anergic B cells is important to identify them and understand their contribution to immune regulation or autoimmune diseases. We report here that a low-level expression of CD138 in the splenic B cells marks naturally arising anergic B cells, not plasma cells. The CD138 int B cells consisted of IgM low IgD high follicular (FO) B cells and transitional 3 B cells in homeostatic conditions. The CD138 int FO B cells showed an anergic gene expression profile shared with that of monoclonal anergic B cells expressing engineered BCRs and the gene expression profile was different from those of plasma cells, age-associated B cells, or germinal center B cells. The anergic state of the CD138 int FO B cells was confirmed by attenuated Ca 2+ response and failure to upregulate CD69 upon BCR engagement with anti-IgM, anti-IgD, anti-Igκ, or anti-IgG. The BCR repertoire of the CD138 int FO B cells was distinct from that of the CD138 − FO B cells and included some class-switched B cells with low-level somatic mutations. These findings demonstrate the presence of polyclonal anergic B cells in the normal mice that are characterized by low-level expression of CD138, IgM downregulation, reduced Ca 2+ and CD69 responses upon BCR engagement, and distinct BCR repertoire.

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CD39 and CD326 Are Bona Fide Markers of Murine and Human Plasma Cells and Identify a Bone Marrow Specific Plasma Cell Subpopulation in Lupus

Cited by 10 publications

References 66 publications

Hydroxychloroquine induces apoptosis of myeloid-derived suppressor cells via up-regulation of CD81 contributing to alleviate lupus symptoms

Hydroxychloroquine induces apoptosis of myeloid-derived suppressor cells via up-regulation of CD81 contributing to alleviate lupus symptoms

Thymus Antibody-Secreting Cells Represent a Tissue Specific Population That Possess an Activated Cellular Phenotype

Low-Level Expression of CD138 Marks Naturally Arising Anergic B Cells

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