OBJECTIVE: To delineate the mechanism of the abnormalities in B cell biology found in patients with primary Sjögren's syndrome (SS). METHODS: The distribution of peripheral B cell subpopulations in 21 patients with primary SS was analyzed by immunofluorescence labeling and flow cytometry. Immunoglobulin rearrangements were analyzed in single B cells isolated from the peripheral blood and parotid glands by fluorescence-activated cell sorting. RESULTS: A significant reduction in the number of peripheral CD27+ memory B cells was found in SS patients, including a significantly reduced number of CD27+/IgD+/IgM+/CD5+ memory B cells. Remarkably, SS patients with secondary lymphoma uniquely exhibited an increase in CD27-expressing peripheral B cells, including CD27(high) plasmablasts. Molecular analysis for mutated Ig gene rearrangements confirmed that CD27 expression distinguished naive and memory cells in SS. In contrast to the peripheral blood, the majority of parotid B cells from 1 patient examined exhibited both the mutational status and phenotype of memory B cells. Accordingly, the mutational frequencies of V(H) rearrangements were significantly greater in parotid B cells than in peripheral blood B cells, whereas the V(H) gene repertoire appeared to be very similar between the compartments. CONCLUSION: These data indicate that there is an accumulation/retention of memory B cells in the inflamed salivary glands of SS patients. It is possible that preferential accumulation of CD27+ memory B cells in the inflamed parotid gland explains their reduction in the peripheral blood.
OBJECTIVE: To delineate the mechanism of the abnormalities in B cell biology found in patients with primary Sjögren's syndrome (SS). METHODS: The distribution of peripheral B cell subpopulations in 21 patients with primary SS was analyzed by immunofluorescence labeling and flow cytometry. Immunoglobulin rearrangements were analyzed in single B cells isolated from the peripheral blood and parotid glands by fluorescence-activated cell sorting. RESULTS: A significant reduction in the number of peripheral CD27+ memory B cells was found in SS patients, including a significantly reduced number of CD27+/IgD+/IgM+/CD5+ memory B cells. Remarkably, SS patients with secondary lymphoma uniquely exhibited an increase in CD27-expressing peripheral B cells, including CD27(high) plasmablasts. Molecular analysis for mutated Ig gene rearrangements confirmed that CD27 expression distinguished naive and memory cells in SS. In contrast to the peripheral blood, the majority of parotid B cells from 1 patient examined exhibited both the mutational status and phenotype of memory B cells. Accordingly, the mutational frequencies of V(H) rearrangements were significantly greater in parotid B cells than in peripheral blood B cells, whereas the V(H) gene repertoire appeared to be very similar between the compartments. CONCLUSION: These data indicate that there is an accumulation/retention of memory B cells in the inflamed salivary glands of SS patients. It is possible that preferential accumulation of CD27+ memory B cells in the inflamed parotid gland explains their reduction in the peripheral blood.
Authors: M Margarida Souto-Carneiro; Vijayabhanu Mahadevan; Kazuki Takada; Ruth Fritsch-Stork; Toshihiro Nanki; Margaret Brown; Thomas A Fleisher; Mildred Wilson; Raphaela Goldbach-Mansky; Peter E Lipsky Journal: Arthritis Res Ther Date: 2009-06-05 Impact factor: 5.156