T cell receptor repertoire in B cell lymphoproliferative lesions in primary Sjogren's syndrome

Objective. Studies have analyzed T cell receptor (TCR)-V beta in benign, minor salivary or lacrimal gland, or kidney lesions in Sjogren's syndrome (SS), We investigated SS related lymphoproliferative lesions. Methods. By "family" reverse transcriptase polymerase chain reaction, we studied the expression of 20 different TCR-V beta families in parotid lymphoproliferative lesions and peripheral blood lymphocytes (PBL) from 7 patients with primary SS, in PBL from 6 primary SS patients with no associated lymphoproliferative disorder, and in activated PBL from 2 healthy controls. T cell clonal expansion was investigated in 10 V beta families (i.e., the most expanded ones and those previously implicated in SS pathogenesis) by single strand conformation polymorphism (SSCP) analysis. Frozen sections from parotid gland specimens were tested by immunohistochemistry for the expansion of selected V beta families. Viral infection within the parotid lesions and serum autoantibody response were also studied. Results, An unrestricted V beta pattern was observed. The most widely expressed V beta family in parotid lesions was V beta 2, and V beta immunohistochemistry results were concordant with V beta mRNA findings. A similar pattern was observed in PBL, although the V beta 2 family was expressed at lower levels. The parotid/PBL ratio was occasionally > 1.8-2.0 (indicative of local V beta overexpression) in different V beta families. T cell expansion proved to be largely polyclonal by SSCP analysis, and scattered T cell clonotypes were detected within different V beta families, with a different pattern from patient to patient. Conclusion. Our observations in SS related lymphoproliferative lesions largely reflect previous evidence in fully benign lesions. The pathogenetic events involved in autoimmune benign lesions in SS may then persist and play a role in SS related lymphoproliferative disorders. The link between the observed TCR-VD repertoire and specific local triggering (auto)antigens remains to be elucidated.