Expanded CD23+/CD21hi B Cells in Inflamed Lymph Nodes Are Associated with the Onset of Inflammatory-Erosive Arthritis in TNF-Transgenic Mice and Are Targets of Anti-CD20 Therapy

Li, Jie; Kuzin, Igor; Moshkani, Safiehkhatoon; Proulx, Steven T.; Xing, Lianping; Skrombolas, Denise; Dunn, Robert R.; Sanz, Iñaki; Schwarz, Edward M.; Bottaro, Andrea

doi:10.4049/jimmunol.0903489

Cited by 75 publications

(161 citation statements)

References 41 publications

(60 reference statements)

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“…These results of the lymph node analyses differ from those in a previous study on peripheral blood, in which gene expression profiling of at risk individuals revealed a low B-cell signature especially in those individuals who developed arthritis after follow-up 20. It is tempting to speculate that the B cells are retained in the lymph nodes, to ensure maturation and differentiation during the immune response which would be in line with findings in animal models of arthritis 12 13…”

Section: Discussioncontrasting

confidence: 44%

The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis

et al. 2013

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ObjectivesRheumatoid arthritis (RA) is an immune-mediated inflammatory disease of unknown aetiology. Recent work has shown that systemic autoimmunity precedes synovial inflammation, and animal models have suggested that changes in the lymph nodes may precede those in the synovial tissue. Therefore, we investigated the cellular composition of the lymph node in the earliest phases of inflammatory arthritis.MethodsThirteen individuals positive for immunoglobulin M (IgM) rheumatoid factor and/or anticitrullinated protein antibodies without arthritis were included. Additionally, we studied 14 early arthritis patients (arthritis duration ≤6 months, naïve for disease-modifying antirheumatic drugs), and eight healthy controls. All subjects underwent ultrasound-guided inguinal lymph node biopsy. Different T- and B-lymphocyte subsets were analysed by multicolour flow cytometry.ResultsThere was an increase in activated CD69 CD8 T cells and CD19 B cells in early arthritis patients compared with healthy controls. We also observed a trend towards increased CD19 B cells in autoantibody-positive individuals without arthritis compared with healthy controls.ConclusionsThis exploratory study suggests that there is increased immune cell activation within lymph nodes of early arthritis patients as well as in autoantibody-positive individuals at risk of developing RA. This method provides a unique tool to investigate immunological changes in the lymph node compartment in the earliest phases of inflammatory arthritis.

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Section: Discussioncontrasting

confidence: 44%

The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis

et al. 2013

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“…Even though this model differs from human RA due to the initiating role of TNF-α and the absence of detectable rheumatoid factor, it does incorporate a number of features relevant to human rheumatoid arthritis [74]. Despite the lack of rheumatoid factor, hTNF-tg mice develop disease-associated B cell changes, and B cell depletion is protective [75]. Further, hTNF-tg mice develop a complex proinflammatory cytokine response with upregulation of interleukin-1 (IL-1) and interleukin-6 (IL-6) that occurs in conjunction with the development of early lesions [16].…”

Section: Tnf-α Driven Modelsmentioning

confidence: 99%

Histopathology in Mouse Models of Rheumatoid Arthritis

Caplazi¹,

Diehl²

2014

Methods in Pharmacology and Toxicology

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Murine models of rheumatoid arthritis are widely used for mechanistic studies and for the validation of therapeutic targets. Many models exist and can be classified into induced and spontaneous types. Even though models vary considerably in the pathogenesis of lesions, overlapping spectra of morphological features render the commonly used models suitable for standard histopathological examination and scoring strategies.

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“…The following antibodies were used for staining of the lung sections: ␣SMA (1:100) (Sigma-Aldrich, St. Louis, MO) 19,20 ; phosphoP38 (1:50), phosphoJNK (1:100), and phosphoERK (1:100) (Cell Signaling Technology, Danvers, MA) 21,22 ; Ki-67 (1:100) (Epitomics, Burlingame, CA) 23,24 ; and VEGF (1:100) (Novus Biologicals, Littleton, CO). 25 Immunohistochemical staining was performed according to our previously described method.…”

Section: Immunohistochemistrymentioning

confidence: 99%

Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung

Shields

Panzhinskiy

Burns

et al. 2011

The American Journal of Pathology

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Expanded CD23+/CD21hi B Cells in Inflamed Lymph Nodes Are Associated with the Onset of Inflammatory-Erosive Arthritis in TNF-Transgenic Mice and Are Targets of Anti-CD20 Therapy

Abstract: Material

Cited by 75 publications

References 41 publications

The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis

The cellular composition of lymph nodes in the earliest phase of inflammatory arthritis

Histopathology in Mouse Models of Rheumatoid Arthritis

Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung

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