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OP0079 Salivary Gland Epithelial Cells (SGECS) Promote the Differentiation of B Cells
  1. A. Morva1,
  2. E. K. Kapsogeorgou1,
  3. O. D. Konsta1,
  4. H. M. Moutsopoulos1,
  5. A. G. Tzioufas1
  1. 1Pathophysiology, School of Medicine, National University of Athens, ATHENS, Greece

Abstract

Background SGECs have been shown to possess a key regulatory role in the inflammatory responses of patients with Sjögren’s syndrome (SS). Emerging studies present evidence for their capacity to participate in the recruitment and activation of immune cells, including the expression of several cytokines and chemokines, adhesion molecules and receptors implicated in innate immunity. Most importantly, SGECs have been shown to mediate T cell activation. Several studies showing the expression of BAFF molecules in SGECs suggest that these might implicated in B cell activation and differentiation.

Objectives To investigate the ability of SGECs to mediate the activation and differentiation of B cells.

Methods Human B cells were purified by negative isolation from PBMCs of healthy donors obtained from leukocyte depletion filters. Resting B cells were cultured alone or with SGEC lines from SS patients (n=6) and non-SS controls (n=6) for 4 days in conditions enabling cell-to-cell contact or in transwell systems permitting interactions only through soluble factors. B cell activation and differentiation were analyzed by flow cytometry evaluating the surface expression of CD40, CD80, CD86, BAFF receptor (CD268), CD38, IgD, CD24, CD21, CD23, CD5 and CD27. Mann-Whitney test was employed to analyze statistical significances.

Results Cell-to-cell interactions between B cells and SGECs resulted in a slight, but definite, increase of the surface expression of CD40 and BAFF receptor molecule on B cells, indicating that SGEC may have an activation effect on B cells. The analysis of CD38/IgD expression revealed that cell-to-cell contact also promoted a switch in B cell differentiation to the Bm5p and Bm2 phenotype, followed by a decrease in the Bm1 subpopulation. This effect was more profound in B cells co-cultured with SGECs from SS patients, rather than those from controls. Similarly, the percentage of Bm1 subpopulation was found to decline, whereas this of Bm5 to augment in transwell systems, supporting the implication of soluble mediators in B cell differentiation. Nevertheless, this effect was not found to differ between SGECs from SS and control patients. Co-culture with SGECs also promoted a transitional type 2-like phenotype of B cells, as assessed by CD38+/CD24+ expression. This was more evident in B cells cultured with SGECs from control patients, even though it was not found to be statistically different from those co-cultured with SS-SGECs. The percentage of CD21+/CD23+-B cell subpopulation was augmented by culture with SGECs, particularly those obtained from controls. Furthermore, a decrease of the CD21+/CD23- subpopulation (marginal zone B cells) was observed in transwell systems; with similar profile between SGECs from SS and control patients. On the other hand, a decrease of CD21-/CD23--B cells (transitional type 1 phenotype) has been observed in cell-to-cell contact co-cultures with SGECs, whereas the opposite effect was observed in transwell co-culture systems. Finally, co-culture with SGECs, including both cell-to-cell contact and soluble mediators, has been found to reduce the CD5+ B cell subpopulation.

Conclusions Our findings suggest that SGECs are capable to drive the activation and differentiation of B cells. Further studies are needed to clarify the importance of these changes in local immune responses.

Disclosure of Interest None Declared

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