Project R-7361

Defining how a novel B cell population contributes to MS pathology (Research)

We hypothesize that the aged B cell compartment is increased in a proportion of MS patients and that it contributes to neuroinflammation in MS through autoreactive and proinflammatory activity. However, the fundamental characteristics of this novel B cell population, in terms of their antigen experience, are entirely unexplored. Thus, the aim of this proposal is to define the (i) origin, (ii) maturation status and (iii) clonal properties of these aged B cell populations in MS patients through next-generation sequencing of the B cell antibody repertoire. The molecular characterization will allow us to determine (i) their origin-whether these B cells develop with or without antigen and germinal center experience and (ii) maturation status-describing characteristics of antigen experience (somatic mutation & class switching) and (iii) clonal repertoire- whether these B cells are represented by a diverse set of clones or are restricted by a limited number of large clonal populations.

01 April 2016 - 31 March 2017