Role of B cells in systemic lupus erythematosus and rheumatoid arthritis

Mandik-Nayak, Laura; Ridge, Natalie A.; Fields, Michele L.; Park, Audrey Y; Erikson, Jan

doi:10.1016/j.coi.2008.08.003

Cited by 26 publications

(16 citation statements)

References 60 publications

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“…Alterations in B cell immune tolerance are increasingly recognized as an important factor in the development of autoimmune rheumatoid arthritis (reviewed in [1]. Developing B cells undergo multiple consecutive tolerance checkpoints (clonal deletion, receptor editing and receptor “tuning” also known as clonal anergy ) that are responsible for the formation of immune tolerance by eliminating or silencing of self-reactive clones.…”

Section: Introductionmentioning

confidence: 99%

Rheumatoid arthritis is associated with signaling alterations in naturally occurring autoreactive B-lymphocytes

Liubchenko

Appleberry

Striebich

et al. 2013

Journal of Autoimmunity

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Immune tolerance established during the development of B lymphocytes can be subverted in mature cells and lead to autoimmunity. This study focuses on the recently discovered subset of CD19+CD27−IgD+IgMlow/− B cells that recognize self-antigens and have the capacity to produce autoantibodies, but under normal conditions do not generate autoimmune response due to intrinsic signaling inhibition (a condition known as clonal anergy and characterized by impaired antigen receptor signaling). Phosphorylation of intracellular signaling proteins and Ca2+ responses in anergic B cells were measured by multicolor flow cytometry. Our results demonstrate a distinct phosphoryation pattern for major signal transduction proteins, which distinguishes anergic B cells. Comparison of B cell signaling properties in Rheumatoid Arthritis patients and healthy controls revealed a reversal of pTyr and Ca2+ anergic signaling features in patients, accompanied by phosphorylation decreases of Blnk, Syk, SHP2, CD19. We identified BCR signaling pathway alterations associated with the loss of anergic B cell tolerance in Rheumatoid Arthritis.

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Section: Introductionmentioning

confidence: 99%

Rheumatoid arthritis is associated with signaling alterations in naturally occurring autoreactive B-lymphocytes

Liubchenko

Appleberry

Striebich

et al. 2013

Journal of Autoimmunity

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“…RA is one of the first autoimmune diseases in which B cell involvement was postulated based on autoantibody production, only to later fall in disfavor because of a lack of direct correlation between autoantibodies and pathogenesis (9–11). However, the recent success of B cell depletion therapy in RA patients refractory to other therapies has rekindled interest in the role of B cells in this disease (12–14).…”

Section: Introductionmentioning

confidence: 99%

CD23+CD21highCD1dhigh B Cells in Inflamed Lymph Nodes Are a Locally Differentiated Population with Increased Antigen Capture and Activation Potential

Moshkani

Kuzin

Adewale

et al. 2012

The Journal of Immunology

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CD23+CD21highCD1dhigh B cells (Bin cells) accumulate in the LNs draining inflamed joints of the TNFα transgenic (TNFtg) mouse model of rheumatoid arthritis, and are primarily involved in the significant histological and functional LN alterations that accompany disease exacerbation in this strain. Here we investigate the origin and function of Bin cells. We show that adoptively transferred GFP+ sorted mature follicular B (FoB) cells home preferentially to inflamed LNs of TNFtg mice where they rapidly differentiate into Bin cells, with a close correlation with the endogenous Bin fraction. Bin cells are also induced in wild-type (WT) LNs after immunization with T-dependent antigens, and display a germinal center phenotype at higher rates compared to FoB cells. Furthermore, we show that Bin cells can capture and process antigen immune complexes in a CD21-dependent manner more efficiently than FoB cells, and express higher levels of MHCII and costimulatory antigens CD80 and CD86. We propose that Bin cells are a previously unrecognized inflammation-induced B cell population with increased antigen capture and activation potential, which may facilitate normal immune responses but may contribute to autoimmunity when chronic inflammation causes their accumulation and persistence in affected LNs.

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“…Significant evidence supports the pathogenic role of autoreactive B cells in Rheumatoid arthritis (RA) [3], [4], [5], [6], [7], [8]. B cell targeted therapies are effective in RA (reviewed in [6], [9], [10]).…”

Section: Introductionmentioning

confidence: 99%

B Cell Receptor Signaling-Based Index as a Biomarker for the Loss of Peripheral Immune Tolerance in Autoreactive B Cells in Rheumatoid Arthritis

Lyubchenko

Zerbe

2014

PLoS ONE

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This study examines the loss of peripherally induced B cell immune tolerance in Rheumatoid arthritis (RA) and establishes a novel signaling-based measure of activation in a subset of autoreactive B cells - the Induced tolerance status index (ITSI). Naturally occurring naïve autoreactive B cells can escape the “classical” tolerogenic mechanisms of clonal deletion and receptor editing, but remain peripherally tolerized through B cell receptor (BCR) signaling inhibition (postdevelopmental “receptor tuning” or anergy). ITSI is a statistical index that numerically determines the level of homology between activation patterns of BCR signaling intermediaries in B cells that are either tolerized or activated by auto antigen exposure, and thus quantifies the level of peripheral immune tolerance. The index is based on the logistic regression analysis of phosphorylation levels in a panel of BCR signaling proteins. Our results demonstrate a new approach to identifying autoreactive B cells based on their BCR signaling features.

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Role of B cells in systemic lupus erythematosus and rheumatoid arthritis

Cited by 26 publications

References 60 publications

Rheumatoid arthritis is associated with signaling alterations in naturally occurring autoreactive B-lymphocytes

Rheumatoid arthritis is associated with signaling alterations in naturally occurring autoreactive B-lymphocytes

CD23+CD21highCD1dhigh B Cells in Inflamed Lymph Nodes Are a Locally Differentiated Population with Increased Antigen Capture and Activation Potential

B Cell Receptor Signaling-Based Index as a Biomarker for the Loss of Peripheral Immune Tolerance in Autoreactive B Cells in Rheumatoid Arthritis

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