Aberrant expression of BAFF by B lymphocytes infiltrating the salivary glands of patients with primary Sjögren's syndrome.
OBJECTIVE
To identify the cells that produce BAFF in the salivary glands of patients with primary Sjögren's syndrome (SS), and to analyze BAFF receptor expression by local T and B lymphocytes.


METHODS
We used 3 methods to identify the source of BAFF: in situ hybridization of the transcripts for BAFF combined with staining of membrane markers, regular and real-time reverse transcription-polymerase chain reaction (RT-PCR) of cultured epithelial cells, and RT-PCR of sorted single-cell T and B lymphocytes eluted from salivary glands. Cells expressing TACI, BCMA, and B lymphocyte stimulator receptor 3 (BR-3) were disclosed by combining each specific staining of the receptors with each specific staining of the cells. The function of BAFF generated by epithelial cells on B lymphocytes was determined in short-term cocultures.


RESULTS
Transcripts for BAFF were seen in epithelial cells and infiltrating T lymphocytes and, for the first time, were detected in local B cells. It is interesting that BR-3 was present on these B cells but not on T cells. In contrast, TACI and, to a lesser degree, BCMA were observed on transitional B lymphocytes, whereas T lymphocytes were devoid of receptors for BAFF. Furthermore, this cytokine was shown to be functional, in that epithelial cell-bound BAFF extended the survival of normal B cells, but cell-free BAFF released in the supernatants did not.


CONCLUSIONS
These experiments establish that in primary SS, BAFF is produced not only by epithelial cells and T cells but also by B cells. The expression of receptors for BAFF would thus allow these receptors to participate in an autocrine pattern of self-stimulation.
Daridon
Capucine
C
Laboratory of Immunology, Brest University Medical School Hospital, Brest, France.
Devauchelle
Valérie
V
Hutin
Pascal
P
Le Berre
Rozenn
R
Martins-Carvalho
Christine
C
Bendaoud
Boutahar
B
Dueymes
Maryvonne
M
Saraux
Alain
A
Youinou
Pierre
P
Pers
Jacques-Olivier
JO
D000328:Adult; D000368:Aged; D053264:B-Cell Activating Factor / Q000096:biosynthesis* / Q000235:genetics; D053301:B-Cell Maturation Antigen / Q000235:genetics / Q000378:metabolism; D001402:B-Lymphocytes / Q000378:metabolism* / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005260:Female; D019084:Fluorescent Antibody Technique, Indirect; D015870:Gene Expression; D006801:Humans; D017403:In Situ Hybridization; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012469:Salivary Glands / Q000033:anatomy & histology / Q000378:metabolism* / Q000473:pathology; D012859:Sjogren's Syndrome / Q000378:metabolism* / Q000473:pathology; D013601:T-Lymphocytes / Q000378:metabolism / Q000473:pathology; D053303:Transmembrane Activator and CAML Interactor Protein / Q000235:genetics / Q000378:metabolism; D020298:U937 Cells
D053264:B-Cell Activating Factor; D053301:B-Cell Maturation Antigen; C465019:BR-3 protein, human; D015415:Biomarkers; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C108467:TNFRSF13B protein, human; C086966:TNFRSF17 protein, human; C505719:TNFSF13B protein, human; D053303:Transmembrane Activator and CAML Interactor Protein