Ectopic Germinal Centers Are Rare in Sjogren's Syndrome Salivary Glands and Do Not Exclude Autoreactive B Cells

被引:133
作者
Le Pottier, Laetitia [1 ,2 ,3 ]
Devauchelle, Valerie [1 ,2 ,3 ,4 ]
Fautrel, Alain [5 ,6 ,7 ]
Daridon, Capucine [1 ,2 ,3 ]
Saraux, Alain [1 ,2 ,3 ,4 ]
Youinou, Pierre [1 ,2 ,3 ,4 ]
Pers, Jacques-Olivier [1 ,2 ,3 ,4 ]
机构
[1] Brest Univ, Equipe Accueil 2216, F-29609 Brest, France
[2] Brest Univ, Inst Fed Rech 418, F-29609 Brest, France
[3] Univ Europeenne Bretagne, Brest, France
[4] CHU Brest, F-29285 Brest, France
[5] Univ Rennes 1, INSERM, U620, Rennes, France
[6] Univ Rennes 1, Inst Fed Rech Core Histopathol Platform 140, Rennes, France
[7] Univ Europeenne Bretagne, Rennes, France
关键词
INDUCED CYTIDINE DEAMINASE; SYSTEMIC-LUPUS-ERYTHEMATOSUS; CLASS-SWITCH RECOMBINATION; MARGINAL ZONE; FUNCTIONAL-HETEROGENEITY; SPHINGOSINE; 1-PHOSPHATE; AUTOIMMUNE-DISEASE; LYMPHOID FOLLICLES; EXPRESSION; BAFF;
D O I
10.4049/jimmunol.0803588
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
This study reports on the characterization of B cells of germinal center (GC)-like structures infiltrating the salivary glands (SGs) of patients with Sjogren'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 Sjogren'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 I-phosphate receptor I 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 Journal of Immunology, 2009, 182: 3540-3547.
引用
收藏
页码:3540 / 3547
页数:8
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