Apoptotic B cells: their interactions with macrophages and modulation by rituximab

Herrington, Felicity (2014) Apoptotic B cells: their interactions with macrophages and modulation by rituximab. PhD thesis, University of Glasgow.

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Abstract

Apoptotic cells (AC) are able to modulate the immune system, dampening inflammation and triggering anti-inflammatory responses by various immune cells as a consequence of interaction and uptake. Rituximab (RTX) is an anti-CD20 monoclonal antibody used as a treatment in several autoimmune diseases, including rheumatoid arthritis (RA). Treatment results in B cell depletion, with B cell apoptosis known to contribute to RTX-mediated B cell death. However the simple removal of B cells from the system does not seem to account for all the beneficial effects of this biologic. We propose that RTX treatment in RA results in the re-establishment of temporary tolerance to the system, through an apoptotic B cell-dependent mechanism. Initial in vitro and in vivo investigations were undertaken to explore the validity of this hypothesis. The present work sought to examine the immunomodulatory capacity of apoptotic B cells and to determine whether the potential anti-inflammatory effects of apoptotic B cells are modulated by RTX, with both in vitro methods and an in vivo model of autoimmunity utilized in these studies. The results presented in this thesis demonstrate that apoptotic B cells have comparable effects on bone marrow derived macrophage (BMDM) phenotype and function in vitro as previously described AC from other cellular sources. Surprisingly, in the in vitro assay system used, viable cells had the same immunomodulatory effects on BMDM as AC, for all criteria investigated. Preliminary studies indicate this may be a promising avenue of inquiry, however further work is needed before a conclusion can be reached as to the relative level of involvement of apoptotic B cell-mediated tolerance in the improvement seen on RTX treatment in RA.

Item Type: Thesis (PhD)
Qualification Level: Doctoral
Keywords: B cells, Rituximab, Apoptosis, Macrophages, Rheumatoid Arthritis
Subjects: Q Science > QR Microbiology > QR180 Immunology
Colleges/Schools: College of Medical Veterinary and Life Sciences > Institute of Infection Immunity and Inflammation > Immunology
Funder's Name: UNSPECIFIED
Supervisor's Name: Goodyear, Dr Carl
Date of Award: 2014
Depositing User: Miss Felicity DeBari Herrington
Unique ID: glathesis:2014-5330
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 11 Jul 2014 13:55
Last Modified: 11 Jul 2014 13:56
URI: http://theses.gla.ac.uk/id/eprint/5330

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