B cells in Sjögren's syndrome: indications for disturbed selection and differentiation in ectopic lymphoid tissue.
Primary Sjögren's syndrome (pSS) is an autoimmune disorder characterized by specific pathological features. A hallmark of pSS is B-cell hyperactivity as manifested by the production of autoantibodies, hypergammaglobulinemia, formation of ectopic lymphoid structures within the inflamed tissues, and enhanced risk of B-cell lymphoma. Changes in the distribution of peripheral B-cell subsets and differences in post-recombination processes of immunoglobulin variable region (IgV) gene usage are also characteristic features of pSS. Comparison of B cells from the peripheral blood and salivary glands of patients with pSS with regard to their expression of the chemokine receptors CXCR4 and CXCR5, and their migratory capacity towards the corresponding ligands, CXCL12 and CXCL13, provide a mechanism for the prominent accumulation of CXCR4+ CXCR5+ memory B cells in the inflamed glands. Glandular B cells expressing distinct features of IgV light and heavy chain rearrangements, (re)circulating B cells with increased mutations of cmu transcripts in both CD27- and CD27+ memory B-cell subsets, and enhanced frequencies of individual peripheral B cells containing IgV heavy chain transcripts of multiple isotypes indicate disordered selection and incomplete differentiation processes of B cells in the inflamed tissues in pSS. This may possibly be related to a lack of appropriate censoring mechanisms or different B-cell activation pathways within the ectopic lymphoid structures of the inflamed tissues. These findings add to our understanding of the pathogenesis of this autoimmune inflammatory disorder and may result in new therapeutic approaches.
Hansen
Arne
A
Charite Center (CC) 12, Department of Medicine, Charité-Universitätsmedizin Berlin, Charité-Platz 01, 10098 Berlin, Germany. arne.hansen@charite.de
Lipsky
Peter E
PE
Dörner
Thomas
T
D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation; D002633:Chemotaxis; D002828:Choristoma / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D006801:Humans; D016131:Lymphocyte Subsets / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008221:Lymphoid Tissue; D054387:Receptors, CXCR / Q000276:immunology / Q000378:metabolism; D012469:Salivary Glands / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D012793:Sialadenitis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D012859:Sjogren's Syndrome / Q000276:immunology* / Q000378:metabolism / Q000473:pathology
D054387:Receptors, CXCR
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