CD83 regulates lymphocyte maturation, activation and homeostasis

Breloer, Minka; Fleischer, Bernhard

doi:10.1016/j.it.2008.01.009

Cited by 99 publications

(94 citation statements)

References 66 publications

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“…3 and 4), it is tempting to speculate that engagement of CD83 on the B cells themselves would modulate their function. However, because CD83 is not exclusively expressed by B cells, but by many activated leukocytes (27), it is likely that anti-CD83 mAb binds to all of these CD83-positive cell types in vivo. To identify the CD83-positive cell population responsible for the biologic effect of CD83 engagement, we generated mixed bone marrow chimeras in which selectively B cells (Fig.…”

Section: Engagement Of Cd83 Specifically On B Cells and Not On DC Modmentioning

confidence: 99%

“…Furthermore, this phenotype was also visible in vitro: purified CD83tg B cells displayed reduced Ig responses and calcium signaling upon in vitro activation, whereas CD83-deficient B cells displayed the reciprocal phenotype (6). These findings had led us to hypothesize that activationinduced CD83 negatively regulates B cells (27), thus contributing to the various mechanisms of negative regulation by receptors such as CD22 (29,30) and CD72 (31) that counteract BCR-mediated signal transduction (32).…”

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confidence: 99%

“…Recent studies provided evidence that CD83 is also involved in the regulation of B cell maturation, homeostasis, and function (27). CD83 is expressed at low levels by B cells beyond the pre-B cell stage, i.e., once they express a functional BCR.…”

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confidence: 99%

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Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

Kretschmer

Lüthje

Schneider

et al. 2009

The Journal of Immunology

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The transmembrane glycoprotein CD83 is an important regulator of both thymic T cell maturation and peripheral T cell response. Recent studies suggested that CD83 is also involved in the regulation of B cell maturation, activation, and homeostasis. In this study, we show that in vivo overexpression of CD83 dose dependently interfered with the Ig response to thymus-dependent and thymus-independent model Ag immunization. CD83 deficiency, in contrast, which was restricted to B cells in mixed bone marrow chimeras, led to unchanged or even slightly increased Ig responses. Strikingly, the engagement of CD83 that is naturally upregulated on wild-type B cells by injection of anti-CD83 mAb in vivo induced a 100-fold increase in the IgG1 response to immunization. Kinetic analysis revealed that CD83 had to be engaged simultaneously or shortly after the B cell activation through injection of Ag, to modulate the IgG1 secretion. Furthermore, using mixed bone marrow chimeras in which either selectively the B cells or the dendritic cells were CD83 deficient, we demonstrate that anti-CD83 mAb mediated its biologic effect by engaging CD83 on B cells and not on CD11c ؉ dendritic cells. Taken together, we provide strong evidence that CD83 transduces regulatory signals into the very B cell on which it is expressed.

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Section: Engagement Of Cd83 Specifically On B Cells and Not On DC Modmentioning

confidence: 99%

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confidence: 99%

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Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

Kretschmer

Lüthje

Schneider

et al. 2009

The Journal of Immunology

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“…28 However, the reason of a selective tubulin overexpression CD83 is usually expressed in mature dendritic cells 29 and triggers CD4 þ T-cell maturation, but is also expressed by activated B cells and involved in the modulation of B-cell receptor signaling. 30 CD83 has previously been described to be upregulated in Hodgkin and Reed-Sternberg cells of Hodgkin lymphoma. 31 Transgenic overexpression of CD83 in B cells resulted in an upregulation of the major histocompatibility complex II (MHC II) and interleukin 10.…”

Section: Discussionmentioning

confidence: 97%

“…31 Transgenic overexpression of CD83 in B cells resulted in an upregulation of the major histocompatibility complex II (MHC II) and interleukin 10. 30 However, MHC II is shown to be downregulated in a subset of classical Hodgkin lymphoma cases, 32 partly owing to translocations involving the MHC II transactivator (CIITA). 33 Decreased MHC class II expression has been linked to reduced tumor cell immunogenicity.…”

Section: Discussionmentioning

confidence: 99%

A novel immunohistochemical classifier to distinguish Hodgkin lymphoma from ALK anaplastic large cell lymphoma

et al. 2014

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Classical Hodgkin lymphoma and ALK À anaplastic large cell lymphoma share many features like strong CD30 expression and usually loss of B-and T-cell markers. However, their clinical course is dramatically different with curability rates of 490% for classical Hodgkin lymphoma and an unfavorable prognosis for anaplastic large cell lymphoma. Classical Hodgkin lymphoma and ALK À anaplastic large cell lymphoma can usually be distinguished by PAX5 expression in the Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma and expression of cytotoxic molecules in tumor cells of anaplastic large cell lymphoma. However, in some cases the differential diagnosis is difficult owing to absence of established markers. To be able to better classify these cases, we reevaluated gene expression data of microdissected tumor cells of both lymphomas for differentially expressed genes. A classifier was established, comprising four genes strongly expressed in Hodgkin and Reed-Sternberg cells of classical Hodgkin lymphoma (MDC/CCL22, CD83, STAT3, and TUBB2B). Applying this classifier to a test cohort, Hodgkin lymphoma was successfully distinguished from ALK À anaplastic large cell lymphoma with an accuracy of 97% (43/44). MDC/CCL22, CD83, and STAT3 have also been found to be expressed in antigen-presenting cells. Therefore, based on our established classifier, Hodgkin and Reed-Sternberg cells differ from tumor cells of anaplastic large cell lymphoma, which can successfully be applied for practical purposes in histopathologic diagnostics.

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CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis

Thalayasingam

Nair

Skelton

et al. 2018

Arthritis & Rheumatology

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ObjectiveRheumatoid arthritis (RA) is a genetically complex disease of immune dysregulation. This study sought to gain further insight into the genetic risk mechanisms of RA by conducting an expression quantitative trait locus (eQTL) analysis of confirmed genetic risk loci in CD4+ T cells and B cells from carefully phenotyped patients with early arthritis who were naive to therapeutic immunomodulation.Methods RNA and DNA were isolated from purified B and/or CD4+ T cells obtained from the peripheral blood of 344 patients with early arthritis. Genotyping and global gene expression measurements were carried out using Illumina BeadChip microarrays. Variants in linkage disequilibrium (LD) with non‐HLA RA single‐nucleotide polymorphisms (defined as r2 ≥ 0.8) were analyzed, seeking evidence of cis‐ or trans‐eQTLs according to whether the associated probes were or were not within 4 Mb of these LD blocks.ResultsGenes subject to cis‐eQTL effects that were common to both CD4+ and B lymphocytes at RA risk loci were FADS1,FADS2,BLK,FCRL3,ORMDL3,PPIL3, and GSDMB. In contrast, those acting on METTL21B,JAZF1,IKZF3, and PADI4 were unique to CD4+ lymphocytes, with the latter candidate risk gene being identified for the first time in this cell subset. B lymphocyte–specific eQTLs for SYNGR1 and CD83 were also found. At the 8p23 BLK–FAM167A locus, adjacent genes were subject to eQTLs whose activity differed markedly between cell types; in particular, the FAM167A effect displayed striking B lymphocyte specificity. No trans‐eQTLs approached experiment‐wide significance, and linear modeling did not identify a significant influence of biologic covariates on cis‐eQTL effect sizes.ConclusionThese findings further refine the understanding of candidate causal genes in RA pathogenesis, thus providing an important platform from which downstream functional studies, directed toward particular cell types, may be prioritized.

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CD83 regulates lymphocyte maturation, activation and homeostasis

Cited by 99 publications

References 66 publications

Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

Engagement of CD83 on B Cells Modulates B Cell Function In Vivo

A novel immunohistochemical classifier to distinguish Hodgkin lymphoma from ALK anaplastic large cell lymphoma

CD4+ and B Lymphocyte Expression Quantitative Traits at Rheumatoid Arthritis Risk Loci in Patients With Untreated Early Arthritis

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