Depletion of CD20 B cells fails to inhibit relapsing mouse experimental autoimmune encephalomyelitis

Eseberuo Sefia,Gareth Pryce,Ute-Christiane Meier,Gavin Giovannoni,David Baker

doi:10.1016/j.msard.2017.03.013

Eseberuo Sefia, Gareth Pryce + Show 3 more

Open Access

https://doi.org/10.1016/j.msard.2017.03.013

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Abstract

BackgroundMultiple sclerosis (MS) is often considered to be a CD4, T cell-mediated disease. This is largely based on the capacity of CD4 T cells to induce relapsing experimental autoimmune encephalomyelitis (EAE) in rodents. However, CD4-depletion using a monoclonal antibody was considered unsuccessful and relapsing MS responds well to B cell depletion via CD20 B cell depleting antibodies. The influence of CD20 B cell depletion in relapsing EAE was assessed. MethodsRelapsing EAE was induced in Biozzi ABH mice. These were treated with CD20-specific (18B12) antibody and the influence on CD45RA-B220 B cell depletion and clinical course was analysed. ResultsRelapsing EAE in Biozzi ABH failed to respond to the marked B cell depletion induced with a CD20-specific antibody. In contrast to CD20 and CD8-specific antibodies, CD4 T cell depletion inhibited EAE. ConclusionSpinal cord antigen-induced disease in ABH mice is CD4 T cell-dependent. The lack of influence of CD20 B cell depletion in relapsing EAE, coupled with the relatively marginal and inconsistent results obtained in other mouse studies, suggests that rodents may have limited value in understanding the mechanism occurring following CD20 B cell depletion in humans.

Highlights

Multiple sclerosis is the major demyelinating disease of the adult central nervous system (Compston & Coles 2008)
To confirm the B cell depleting capabilities of CD20-specific mAb, 250μg 18B12 mouse IgG2 variant was injected into Biozzi ABH mice and blood and splenocytes sampled at baseline 7, 14 and 21 days post-injection and the numbers of B cells assessed (Figure 1)
ABH mice were injected with CD20 B cell depleting mAb on day 8 prior to the onset of initial acute EAE (Figure 2A)

Summary

Introduction

Multiple sclerosis is the major demyelinating disease of the adult central nervous system (Compston & Coles 2008). It was hypothesized that therapeutic depletion of B cells would inhibit relapsing EAE, in Biozzi ABH mice (Al-Izki et al 2012), surprisingly marked CD20 B cell depletion failed to influence EAE, in contrast to that found in MS. Multiple sclerosis (MS) is often considered to be a CD4, T cell-mediated disease This is largely based on the capacity of CD4 T cells to induce relapsing experimental autoimmune encephalomyelitis (EAE) in rodents. Relapsing EAE was induced in Biozzi ABH mice These were treated with CD20-specific (18B12) antibody and the influence on CD45RA-B220 B cell depletion and clinical course was analysed. Relapsing EAE in Biozzi ABH failed to respond to the marked B cell depletion induced with a CD20-specific antibody. The lack of influence of CD20 B cell depletion in relapsing EAE, coupled with the relatively marginal and inconsistent results obtained in other mouse studies, suggests that rodents may have limited value in understanding the mechanism occurring following CD20 B cell depletion in humans

Methods

Results

Conclusion