To the Editor:

We appreciate the interest in our study on the ability of RTX to mediate CD19 loss from normal human B cells and its inability to mediate complement-dependent cytotoxicity. Using rabbit serum and positively selected B cells, Kamburova et al show that RTX can induce complement-dependent killing. First, we are uncertain as to the relevance of this approach to human biology; we saw no loss of B cells when RTX was added to whole blood for 30 minutes (n = 32) or to PBMCs cultured in 10% normal human serum for 48 hours. Second, we appreciate the notion that detection of different CD19 epitopes might account for their findings but think this is unlikely as our data (as seen in Figure 5 of our article) demonstrate transfer of CD19 to the surface of monocytes and neutrophils. Additionally, investigators at other laboratories have also identified RTX-mediated loss of CD19 using different antibodies (Beum PV, Kennedy AD, Williams ME, Lindofer MA, Taylor RP. The shaving reaction: rituximab/CD20 complexes are removed from mantle cell lymphoma and chronic lymphocytic leukemia cells by THP-1 monocytes. J Immunol 2006;176:2600–9).

Both Kamburova et al and Mei et al state that they saw a reduction in CD19 expression at >2 months in different patient populations. We do not disagree: RTX causes extensive peripheral B cell depletion. We stand by the observation that trogocytosis occurs in vivo as has been reported (Williams MD, Densmore JJ, Pawluczkowycz AW, Beum PV, Kennedy AD, Lindorfer MA, et al. Thrice-weekly low-dose rituximab decreases CD20 loss via shaving and promotes enhanced targeting in chronic lymphocytic leukemia. J Immunol 2006;177:7435–43) and which we have demonstrated in patients with RA (Figure 1). Finally, the fate of B cells subjected to trogocytosis (and therefore deficient in CD20 and CD19 expression) over time remains unknown.

Figure 1.

CD19 levels in the lymphocyte population of PBMCs isolated from whole blood drawn immediately preceding (red) and immediately following (blue) completion of a 1,000 mg intravenous RTX infusion in a patient with rheumatoid arthritis. Results show a significant drop in CD19+ cells, as well as a leftward shift in the mean fluorescence intensity of CD19, indicating emergence of a subpopulation of B cells that have undergone trogocytosis due to the binding of RTX to CD20.

Jonathan D. Jones MD*, B. JoNell Hamilton MS†, William F. C. Rigby MD‡, * Dartmouth-Hitchcock Medical Center, and Geisel School of Medicine at Dartmouth College, Lebanon, NH, † Geisel School of Medicine at Dartmouth College, Lebanon, NH, ‡ Dartmouth-Hitchcock Medical Center, and Geisel School of Medicine at Dartmouth College, Lebanon, NH.