Project R-6426

Effects of immune aging on B cell populations in multiple sclerosis (MS) (Research)

Immunosenescence or aging of the immune system occurs in aged individuals and in a proportion of patients with multiple sclerosis (MS), an inflammatory disorder of the central nervous system (CNS). Humoral immune aging is characterized by a reduced response to infections and increased autoantibody production. Recently, 2 populations of aged B cells with proinflammatory functional characteristics were described, namely IgD-CD27- double negative (DN) B cells and CD21-CD11c+ (CD21-) B cells. Preliminary results indicate the expansion of aged B cells in the peripheral blood of a proportion of MS patients. We hypothesize that aged B cells contribute to MS pathogenesis through autoreactive and proinflammatory effector mechanisms. The proportion of CD21- and DN B cells in the peripheral and intrathecal B cell repertoire in MS patients and controls is determined in a large-scale cohort study. Further characterization of the most promising aged B cell subset is performed by state of the art technology. B cell receptor diversity and the underlying gene pathways are unraveled by next-generation sequencing. Functional validation is done by analyzing autoantibody production and cytokine secretion. This study provides better insights into the effects of aging on humoral immunity in MS. This can lead to the development of novel therapeutic strategies, not only for MS but also for other B cell dependent autoimmune disorders.

01 October 2015 - 13 January 2019