Figure 1

Hypothetical scheme of B-cell differentiation pathways in ectopic lymphoid tissues in primary Sjögren's syndrome. Preactivated peripheral B cells are recruited by chemokines into the microenvironment of chronically inflamed tissues. This microenvironment represents a 'niche' where B cells may escape from peripheral check points against autoreactivity but are abnormally stimulated, proliferate and incompletely differentiate via T-cell-dependent or T-cell-independent pathways into memory B cells and plasma cells. Rheumatoid factor-expressing B cells may be abnormally stimulated by local BAFF excess and locally secreted (auto)antibodies. Abnormal stimulation and impaired censoring mechanisms enhance the risk for malignant transformation of B cells. Emigration and recirculation of B cells that had incomplete differentiation processes contribute to peripheral B-cell disturbances. EC, epithelial cell; FDC, follicular dendritic cell; PC, plasma cell; BAFF, B-cell activating factor; Ig, immunoglobulin.