Failed B cell survival factor trials support the importance of memory B cells in multiple sclerosis. (6th November 2019)

• Record Type: Journal Article
• Authors: Baker, D.; Pryce, G.; James, L. K.; Schmierer, K.; Giovannoni, G.
• Is Part Of: European journal of neurology. Volume 27:Number 2(2020)
• Page Start: 221
• Page End: 228
• Publication Date: 2019-11-06
• Subjects: a proliferating ligand -- B cell activating factor -- memory B cells -- multiple sclerosis -- trial; Neurology -- Periodicals; Nervous system -- Diseases -- Periodicals; 616.8
• DOI: 10.1111/ene.14105
• Languages: English
• ISSNs: 1351-5101

Abstract

Abstract : Clinical trials are probably the most informative experiments to help an understanding of multiple sclerosis (MS) biology. Recent successes with CD20‐depleting antibodies have focused attention towards B cell subsets as important mediators in MS. The trial of tabalumab (NTC00882999), which inhibits B cell activation factor (BAFF), is reported and reviewed and this trial is contrasted with the trial on the inhibition of a proliferation‐inducing ligand (APRIL) and BAFF using atacicept (NCT00642902). Both tabalumab and atacicept induce depletion of mature B cells and inhibit antibody formation, but they fail to deplete memory B cells and do not inhibit relapsing MS. Atacicept is reported to augment memory B cell responses and may precipitate relapse, suggesting the importance of APRIL. However, BAFF inhibition can enhance peripheral blood memory B cell responses, which was not associated with augmented relapse. Although other interpretations are possible, these data further support the hypothesis that memory B cells may be of central importance in relapsing MS, as they are the major CD20+ B cell subset expressing APRIL receptors. They also suggest that quantitative and/or qualitative differences in B cell responses or other factors, such as an immune‐regulatory effect associated with APRIL, may be important in determining whether MS reactivates following neutralization of peripheral B cell maturation and survival factors.