Fc gamma receptor II (FcgRII) in CLL patients.

GAMBERALE ROMINA; BORGE MERCEDES; GIORDANO MIRTA

BLOOD, THE JOURNAL OF THE AMERICAN SOCIETY OF HEMATOLOGY - ONLINE

American society of hematology

Año: 2011 p. 1 - 2

1528-0020

We have read with interest the article by Lim et al 1 analyzing the role of Fc gamma receptor IIb (FcgRIIb) on the promotion of rituximab internalization in different B-cell malignancies including B-cell chronic lymphocytic leukemia (CLL). The authors stated that rituximab internalization correlates with FcgRIIb expression, which was determined by using the monoclonal antibody (mAb) AT.10, a pan-specific mAb for human FcgRII that binds to and blocks both the myeloid FcgRIIa and the inhibitory FcgRIIb. We have previously evaluated the FcgRII isoforms in CLL cells and reported that while leukemic cells from all the patients evaluated express FcgRIIb, a considerable proportion also aberrantly express FcgRIIa on CLL cells 2. By using three different mAbs (whole molecules of AT10, 2E1 or IV.3) we demonstrated that leukemic cells from CLL patients show a heterogeneous surface expression of FcgRII compared to the much more homogeneous expression of healthy B cells 3. By performing RT-PCR from purified CLL cells we have also already reported that FcgRIIb1 and FcgRIIb2 are expressed by leukemic cells 4 and that these receptors are biologically active in CLL, since they effectively diminished BCR-triggered signaling 2. We also evaluated the expression of FcgRIIa in CLL cells by employing the mAb IV.3 which specifically recognizes FcgRIIa when used as Fab fragment 5. We found that half of the CLL patients evaluated aberrantly expressed the myeloid FcgRIIa isoform while, in accordance with previous reports 6, surface FcgRIIa was neither detected in tonsillar nor in circulating B cells from healthy donors 2. Since the expression of FcgRIIa on CLL cells was also heterogeneous 2, in those patients where FcgRIIa was absent or marginally expressed, the staining of the leukemic clone with AT.10 would represent the expression of the inhibitory FcgRIIb. By contrast, in those CLL samples where the expression of FcgRIIa was high 2, AT.10 staining would overestimate FcgRIIb expression of these cells. Lim et al 1 did not mention whether they evaluated FcgRIIa expression on the CLL samples included in the study. Therefore, based on their results and considering that the mAb AT.10 can also be detecting FcgRIIa on leukemic cell surface, they should conclude that FcgRII (but not FcgRIIb) correlates with rituximab internalization in CLL.