BAFF-modulated repopulation of B lymphocytes in the blood and salivary glands of rituximab-treated patients with Sjögren's syndrome

Arthritis Rheum. 2007 May;56(5):1464-77. doi: 10.1002/art.22603.


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 experiments 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 x 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.

Publication types

  • Controlled Clinical Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antibodies, Monoclonal / blood
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents / blood
  • Antirheumatic Agents / therapeutic use*
  • B-Cell Activating Factor / blood
  • B-Cell Activating Factor / physiology*
  • B-Lymphocyte Subsets / pathology
  • B-Lymphocytes / pathology*
  • Biopsy
  • Dose-Response Relationship, Drug
  • Humans
  • Lymphocyte Depletion / methods
  • Rituximab
  • Salivary Glands / immunology
  • Sjogren's Syndrome / drug therapy*
  • Sjogren's Syndrome / pathology


  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Murine-Derived
  • Antirheumatic Agents
  • B-Cell Activating Factor
  • TNFSF13B protein, human
  • Rituximab