title: A single dose of rituximab does not deplete B cells in secondary lymphoid organs but alters phenotype and function.
abstract: A single dose of the anti-CD20 monoclonal antibody rituximab induces a nearly complete B cell depletion in peripheral blood, but not in secondary lymphoid organs. Modulation of this remaining B cell population due to rituximab treatment may contribute to the therapeutic effects of rituximab. To assess the in vivo effects of rituximab we used lymph nodes (LNs) collected during renal transplant surgery in patients who had received rituximab 4 weeks earlier in preparation for an ABO-incompatible transplantation. Rituximab treatment resulted in a lower percentage of naïve (IgD(+)CD27(-)) and a higher percentage of switched memory (IgD(-)CD27(+)) B cells. Remarkably, transitional (CD24(++)CD38(++)) B cells were virtually lacking in the LNs of rituximab-treated patients. Moreover, LN-derived B cells from rituximab-treated patients produced different amounts of various Ig-subclasses after anti-CD40/IL-21 stimulation ex vivo. Finally, after stimulation of allogeneic T cells with LN-derived B cells from rituximab-treated patients, the proliferated T cells showed a decreased production of IL-17. In conclusion, after treatment with rituximab there remains a B cell population with different functional capacities. Consequently, the effect of rituximab on the immune response will not only be determined by the extent of B cell depletion, but also by the functional properties of the remaining B cells.
authors.affiliation: Department of Laboratory Medicine, Medical Immunology, Radboud University Medical Centre, Nijmegen, The Netherlands.
authors.forename: E G
authors.initials: EG
authors.lastname: Kamburova
authors.forename: H J P M
authors.initials: HJ
authors.lastname: Koenen
authors.forename: K J E
authors.initials: KJ
authors.lastname: Borgman
authors.forename: I J
authors.initials: IJ
authors.lastname: ten Berge
authors.forename: I
authors.initials: I
authors.lastname: Joosten
authors.forename: L B
authors.initials: LB
authors.lastname: Hilbrands
mesh_terms: D000328:Adult; D000368:Aged; D058846:Antibodies, Monoclonal, Murine-Derived / Q000008:administration & dosage*; D018951:Antigens, CD20; D001402:B-Lymphocytes / Q000187:drug effects / Q000276:immunology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D005260:Female; D005434:Flow Cytometry; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D007155:Immunologic Factors / Q000008:administration & dosage; D016030:Kidney Transplantation / Q000276:immunology*; D008213:Lymphocyte Activation / Q000187:drug effects* / Q000276:immunology; D008212:Lymphocyte Depletion; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D000069283:Rituximab; D013154:Spleen / Q000187:drug effects / Q000276:immunology* / Q000473:pathology; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000473:pathology
chemical_list: D058846:Antibodies, Monoclonal, Murine-Derived; D018951:Antigens, CD20; D007155:Immunologic Factors; D000069283:Rituximab