Objective. Treatment with rituximab depletes B cells from the peripheral blood (PB) and salivary glands (SGs) of patients with primary Sjögren’s syndrome (SS). The purpose of this study was to track the repopulation of B cell subsets in PB as well as their subsequent homing into SGs in patients with primary SS treated with rituximab.

Methods. A series of 4-color flow cytometry exper-iments delineated B cell subsets in 15 patients with primary SS. All were tested on days 8 and 15 of treatment. Nine of the patients were followed up monthly for 10 months, and the remaining 6 patients were followed up monthly for 24 months. Enzyme-linked immunosorbent assays were developed to measure serum levels of BAFF and rituximab. SGs were biopsied at the start of the study and 4 months after treatment in 15 patients, 12 months after treatment in 3 patients, and 24 months after treatment in 2 patients.

Results. Baseline serum levels of BAFF correlated inversely (r 0.92, P< 5 10 4) with the duration of B cell depletion: the higher the BAFF levels, the shorter the duration of B cell depletion. Four B cell subsets repopulated the PB: plasmablasts (CD19, CD5, IgD, CD38), transitional type 1 (T1) B cells (CD19, CD5, IgD, CD38), mature Bm2 cells (CD19, CD5/, IgD, CD38/), and memory B cells (CD19, CD5, IgD, CD38). Increased numbers of Bm2 cells and decreased memory B cells reappeared with time. Sequential SG biopsies revealed that B cells were absent in these glands for 12 months: they were detected 24 months after rituximab treatment. Memory and T1 B cells were the first B cells identified locally.

Conclusion. The timing of B cell repopulation is modulated by BAFF and is followed by reconstitution of the preexisting abnormalities.