NDLI: Induction of interleukin-6 production by rituximab in human B cells.

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Induction of interleukin-6 production by rituximab in human B cells.

Content Provider	World Health Organization (WHO)-Global Index Medicus
Author	Jones, Jonathan D. Hamilton, B. JoNell Skopelja, Sladjana Rigby, William F. C.
Description	Author Affiliation: Jones JD ( Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.)
Abstract	OBJECTIVE: Rituximab (RTX), an anti-CD20 monoclonal antibody, is highly effective in the treatment of several autoimmune diseases. The mechanism by which RTX treatment improves rheumatoid arthritis and antineutrophil cytoplasmic antibody-associated vasculitis is not easily related to B cell depletion alone. Prior studies have shown that RTX mediates a rapid stripping of CD20 and CD19 from the human B cell through a process known as trogocytosis. The aim of the present study was to investigate whether changes in B cell phenotype resulting from trogocytosis would diminish the ability of B cells to promote autoimmune disease. METHODS: Human peripheral blood mononuclear cells were cultured with RTX under conditions that permitted trogocytosis. Changes in B cell phenotype and cytokine production were measured in the basal state and under conditions of activation with interleukin-4 (IL-4)/anti-CD40. The effects of RTX were characterized in terms of a requirement for interaction with the FcÎ³ receptor (FcÎ³R) and other Fc-dependent interactions. RESULTS: Trogocytosis induced a marked loss of surface CD19, IgD, CD40, and B cell-activating factor receptor, but did not alter induction of CD86 expression on purified B cells following IL-4/anti-CD40 treatment. Unexpectedly, RTX-dependent trogocytosis of normal human B cells in vitro led to a rapid up-regulation of IL-6 production, with no effect on the production of tumor necrosis factor , IL-1ß, interferon-Î³, or IL-10. This effect was Fc-dependent and required the presence of an FcÎ³R-bearing cell. Moreover, this effect involved the release of preformed intracellular IL-6 protein, as well as marked increases in IL-6 messenger RNA levels. CONCLUSION: RTX-mediated trogocytosis of B cells in vitro results in acute production and release of IL-6. The nature of this effect and how it is related to the acute infusion reactions seen with RTX administration remain to be determined.
File Format	HTM / HTML
ISSN	23265191
e-ISSN	23265205
DOI	10.1002/art.38798
Journal	Arthritis & Rheumatology
Issue Number	11
Volume Number	66
Language	English
Publisher	Wiley
Publisher Date	2014-11-01
Publisher Place	United States
Access Restriction	Open
Subject Keyword	Discipline Rheumatology Antibodies, Monoclonal, Murine-derived Pharmacology Antirheumatic Agents B-lymphocytes Drug Effects Metabolism Interleukin-6 Up-regulation Antigens, Cd40 Cells, Cultured Immunoglobulin D In Vitro Techniques Interleukin-10 Interleukin-1beta Interleukin-4 Receptors, Igg Rituximab Tumor Necrosis Factor-alpha Research Support, N.i.h., Extramural Research Support, Non-u.s. Gov't
Content Type	Text
Resource Type	Article
Subject	Immunology and Allergy Immunology Rheumatology

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