Reconstitution of peripheral blood B cells after depletion with rituximab in patients with rheumatoid arthritis

OBJECTIVE: To study the quantitative and phenotypic reconstitution of peripheral blood B cells and its relationship to the dynamics of clinical response in patients with rheumatoid arthritis (RA) following B cell depletion with rituximab. METHODS: Twenty-four patients with active RA treated with rituximab were studied. Flow cytometry with combinations of monoclonal antibodies to B cell and T cell subsets was used. RESULTS: The frequency and total number of CD19+ cells in the peripheral blood decreased a mean of 97% for more than 3 months in all but 1 patient following rituximab therapy. All B cell populations were depleted. More than 80% of residual B cells showed a memory or plasma cell precursor phenotype. B cell repopulation occurred a mean of 8 months after treatment and was dependent on the formation of naive B cells, which showed an increased expression of CD38 and CD5. During repopulation, increased numbers of circulating immature B cells, CD19+,IgD+,CD38(high),CD10(low),CD24(high) cells, were identified. Patients who experienced a relapse of RA on return of B cells tended to show repopulation with higher numbers of memory B cells. A small number of T cells and natural killer cells expressed low levels of CD20. These cells were depleted following rituximab therapy and returned to the circulation a mean of 5 months after treatment. No other significant changes were detected in the T cell populations studied. CONCLUSION: Rituximab induced a profound depletion of all peripheral blood B cell populations in patients with RA. Repopulation occurred mainly with naive mature and immature B cells. Patients whose RA relapsed on return of B cells tended to show repopulation with higher numbers of memory B cells.