In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.

Rituximab is a chimeric anti-CD20 monoclonal antibody (mAb) used in B-cell malignancies, various autoimmune disorders and organ transplantation. Although administration of a single dose of rituximab results in full B-cell depletion in peripheral blood, there remains a residual B-cell population in s...

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Main Authors: Kamburova, E, Koenen, H, Boon, L, Hilbrands, L, Joosten, I
Format: Journal article
Language:English
Published: 2012
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author Kamburova, E
Koenen, H
Boon, L
Hilbrands, L
Joosten, I
author_facet Kamburova, E
Koenen, H
Boon, L
Hilbrands, L
Joosten, I
author_sort Kamburova, E
collection OXFORD
description Rituximab is a chimeric anti-CD20 monoclonal antibody (mAb) used in B-cell malignancies, various autoimmune disorders and organ transplantation. Although administration of a single dose of rituximab results in full B-cell depletion in peripheral blood, there remains a residual B-cell population in secondary lymphoid organs. These nondepleted B cells might be altered by exposure to rituximab with subsequent immunomodulatory effects. Therefore, we analyzed in vitro the effects of rituximab on proliferation, activation and differentiation of CD19(+) B cells by means of carboxyfluorescein succinimidyl ester (CFSE)-based multiparameter flow cytometry. Rituximab inhibited the proliferation of CD27(-) naïve, but not of CD27(+) memory B cells. Interestingly, upon stimulation with anti-CD40 mAb and interleukin-21 in the presence of rituximab there was an enrichment of B cells that underwent only one or two cell divisions and displayed an activated naïve phenotype (CD27(-)IgD(+)CD38(-/+)). The potency of prestimulated B cells to induce T-cell proliferation was increased by exposure of the B cells to rituximab. Of note, after stimulation with rituximab-treated B cells, proliferated T cells displayed a more Th2-like phenotype. Overall, these results demonstrate that rituximab can affect human B-cell phenotype and function, resulting in an altered outcome of B-T cell interaction.
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spelling oxford-uuid:ec9a072b-ed3a-41c9-a36b-dbedf79ddf542022-03-27T11:18:36ZIn vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:ec9a072b-ed3a-41c9-a36b-dbedf79ddf54EnglishSymplectic Elements at Oxford2012Kamburova, EKoenen, HBoon, LHilbrands, LJoosten, IRituximab is a chimeric anti-CD20 monoclonal antibody (mAb) used in B-cell malignancies, various autoimmune disorders and organ transplantation. Although administration of a single dose of rituximab results in full B-cell depletion in peripheral blood, there remains a residual B-cell population in secondary lymphoid organs. These nondepleted B cells might be altered by exposure to rituximab with subsequent immunomodulatory effects. Therefore, we analyzed in vitro the effects of rituximab on proliferation, activation and differentiation of CD19(+) B cells by means of carboxyfluorescein succinimidyl ester (CFSE)-based multiparameter flow cytometry. Rituximab inhibited the proliferation of CD27(-) naïve, but not of CD27(+) memory B cells. Interestingly, upon stimulation with anti-CD40 mAb and interleukin-21 in the presence of rituximab there was an enrichment of B cells that underwent only one or two cell divisions and displayed an activated naïve phenotype (CD27(-)IgD(+)CD38(-/+)). The potency of prestimulated B cells to induce T-cell proliferation was increased by exposure of the B cells to rituximab. Of note, after stimulation with rituximab-treated B cells, proliferated T cells displayed a more Th2-like phenotype. Overall, these results demonstrate that rituximab can affect human B-cell phenotype and function, resulting in an altered outcome of B-T cell interaction.
spellingShingle Kamburova, E
Koenen, H
Boon, L
Hilbrands, L
Joosten, I
In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.
title In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.
title_full In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.
title_fullStr In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.
title_full_unstemmed In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.
title_short In vitro effects of rituximab on the proliferation, activation and differentiation of human B cells.
title_sort in vitro effects of rituximab on the proliferation activation and differentiation of human b cells
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AT hilbrandsl invitroeffectsofrituximabontheproliferationactivationanddifferentiationofhumanbcells
AT joosteni invitroeffectsofrituximabontheproliferationactivationanddifferentiationofhumanbcells