Expansion of Autoreactive Unresponsive CD21−/low B Cells in Sjögren's Syndrome–Associated Lymphoproliferation. Issue 4 (28th March 2013)

• Record Type: Journal Article
• Authors: Saadoun, D.; Terrier, B.; Bannock, J.; Vazquez, T.; Massad, C.; Kang, I.; Joly, F.; Rosenzwajg, M.; Sene, D.; Benech, P.; Musset, L.; Klatzmann, D.; Meffre, E.; Cacoub, P.
• Is Part Of: Arthritis and rheumatism. Volume 65:Issue 4(2013:Apr.)
• Page Start: 1085
• Page End: 1096
• Publication Date: 2013-03-28
• Subjects: Arthritis -- Periodicals; Rheumatism -- Periodicals; Arthritis -- Periodicals; Rheumatic Diseases -- Periodicals; Rhumatisme -- Périodiques; Arthrite -- Périodiques; 616.72
• DOI: 10.1002/art.37828
• Languages: English
• ISSNs: 0004-3591

Abstract

<abstract abstract-type="main" xml:lang="en"> <title>Abstract</title> <sec id="abs1-1" sec-type="section"> <title>Objective</title> <p>Primary Sjögren's syndrome (SS) is an autoimmune disease associated with a high risk of developing non‐Hodgkin's lymphoma. This study was undertaken to determine the nature of B cells driving lymphoproliferation in primary SS.</p> </sec> <sec id="abs1-2" sec-type="section"> <title>Methods</title> <p>B cell subsets and function were analyzed in peripheral blood from 66 adult patients with primary SS (including 14 patients with B cell lymphoproliferative disease [LPD]) and 30 healthy donors, using flow cytometry, calcium mobilization, and gene array analysis. The reactivity of recombinant antibodies isolated from single B cells from patients with primary SS and LPD was tested using an enzyme‐linked immunosorbent assay.</p> </sec> <sec id="abs1-3" sec-type="section"> <title>Results</title> <p>We observed an expansion of an unusual CD21<sup>−/low</sup> B cell population that correlated with lymphoproliferation in patients with primary SS. A majority of CD21<sup>−/low</sup> B cells from patients with primary SS expressed autoreactive antibodies, which recognized nuclear and cytoplasmic structures. These B cells belonged to the memory compartment, since their Ig genes were mutated. They were unable to induce calcium flux, become activated, or proliferate in response to B cell receptor and/or CD40 triggering, suggesting that these autoreactive B cells may be anergic. However, CD21<sup>−/low</sup> B cells from patients with primary SS remained responsive to Toll‐like receptor (TLR) stimulation. Molecules specifically expressed in CD21<sup>−/low</sup> B cells that are likely to induce their unresponsive stage were detected in gene array analyses.</p> </sec> <sec id="abs1-4" sec-type="section"> <title>Conclusion</title> <p>Patients with primary SS who display high frequencies of autoreactive and unresponsive CD21<sup>−/low</sup> B cells are susceptible to developing lymphoproliferation. These cells remain in peripheral blood controlled by functional anergy instead of being eliminated, and chronic antigenic stimulation through TLR stimulation may create a favorable environment for breaking tolerance and activating these cells.</p> </sec> </abstract>