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* Equipe d'Accueil 2216 and Institut Fédératif de Recherche 418, Science et Ingénierie en Biologie-Santé, Université de Brest, Brest, and Université Européenne de Bretagne, Brest, France;
Centre Hospitalier Universitaire de Brest, Brest, France;
Institut National de la Santé et de la Recherche Médicale Unité 620, and Institut Fédératif de Recherche 140 Core Histopathology Platform, Université de Rennes I, and Université Européenne de Bretagne, Rennes, France
This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sjögren’s syndrome. Eight two-color combinations were devised to characterize the phenotype of these B cells in 11 SG specimens selected from biopsies obtained from 40 Sjögren’s syndrome patients and three normal tonsils. The 9G4 mAb, which recognizes V4.34-encoded autoAbs, enabled us to identify autoreactive B cells. Quantitative RT-PCR was used to determine the level of mRNAs for activation-induced cytidine deaminase (AICDA), repressors and transcription factors. CD20+IgD–CD38+CD21+CD24– B cells, similar to those identified in tonsil GCs, were seen in the SGs of four patients and, and since they expressed AICDA, they were termed "real GCs". CD20+IgD+CD38–CD21+CD24+ B cells, seen in aggregates from the remaining seven samples, were characteristically type 2 transitional B cells and marginal zone-type B cells. They lacked AICDA mRNAs and were termed "aggregates". Real GCs from SGs contained mRNAs for Pax-5 and Bcl-6, like tonsil GC cells, whereas aggregates contained mRNAs for Notch-2, Blimp-1, IRF-4, and BR3, similar to marginal zone B cells. Further experimental data in support of this dichotomy included the restriction of CXCR5 expression to real GC cells, while sphingosine 1-phosphate receptor 1 was expressed only in aggregates. In contrast, both types of B cell clusters expressed the idiotype recognized by the 9G4 mAb. Our data indicate that, in SGs, a minority of B cell clusters represent genuine GC cells, while the majority manifest features of being type 2 transitional B cells and marginal zone cells. Interestingly, both types of B cell aggregates include autoreactive B cells.
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
1 This work was supported by the French Ministry for Education and Research.
2 Address correspondence and reprint requests to Dr. Pierre Youinou, Laboratory of Immunology, Brest University Medical School Hospital, BP 824, F29609 Brest, France. E-mail address: youinou{at}univ-brest.fr
3 Abbreviations used in this paper: SS, Sjögren’s syndrome; BT1 and BT2, type 1 and type 2 transitional B cells; BR3, BAFF receptor 3; BAFF, B cell-activating factor of the TNF family; FO, follicle/follicular; FDC, follicular dendritic cell; GC, germinal center; TF, transcription factor; MZ, marginal zone; S1P1, sphingosine 1-phosphate receptor 1; AID, activation-induced cytidine deaminase; PC, plasma cell; SLE, systemic lupus erythematosus; SG, salivary gland; FM, follicular mantle; TRITC, tetramethylrhodamine isothiocyanate; LT, lymphotoxin; AICDA, activation-induced cytidine deaminase.
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  T. R. Reksten, M. V. Jonsson, E. A. Szyszko, J. G. Brun, R. Jonsson, and K. A. Brokstad Cytokine and autoantibody profiling related to histopathological features in primary Sjogren's syndrome Rheumatology, September 1, 2009; 48(9): 1102 - 1106. [Abstract] [Full Text] [PDF]
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