Selective emergence of antibody-secreting cells in the multiple sclerosis brain

Background Although distinct brain-homing B cells have been identified in multiple sclerosis (MS), it is unknown how these further evolve to contribute to local pathology. We explored B-cell maturation in the central nervous system (CNS) of MS patients and determined their association with immunoglobulin (Ig) production, T-cell presence, and lesion formation. Methods Ex vivo flow cytometry was performed on post-mortem blood, cerebrospinal fluid (CSF), meninges and white matter from 28 MS and 10 control brain donors to characterize B cells and antibody-secreting cells (ASCs). MS brain tissue sections were analysed with immunostainings and microarrays. IgG index and CSF oligoclonal bands were measured with nephelometry, isoelectric focusing, and immunoblotting. Blood-derived B cells were cocultured under T follicular helper-like conditions to evaluate their ASC-differentiating capacity in vitro. Findings ASC versus B-cell ratios were increased in post-mortem CNS compartments of MS but not control donors. Local presence of ASCs associated with a mature CD45low phenotype, focal MS lesional activity, lesional Ig gene expression, and CSF IgG levels as well as clonality. In vitro B-cell maturation into ASCs did not differ between MS and control donors. Notably, lesional CD4+ memory T cells positively correlated with ASC presence, reflected by local interplay with T cells. Interpretation These findings provide evidence that local B cells at least in late-stage MS preferentially mature into ASCs, which are largely responsible for intrathecal and local Ig production. This is especially seen in active MS white matter lesions and likely depends on the interaction with CD4+ memory T cells.

Automated summary

In this study, researchers explored the maturation of B cells in the central nervous system (CNS) of multiple sclerosis (MS) patients and their association with immunoglobulin production, T-cell presence, and lesion formation. They found that local antibody-secreting cells (ASCs) were associated with mature B cells, focal MS lesions, and increased levels of IgG in the cerebrospinal fluid (CSF). Additionally, they discovered a positive correlation between the presence of ASCs and CD4+ memory T cells in MS lesions. These findings suggest that local B cells in late-stage MS preferentially mature into ASCs, which contribute to intrathecal and local Ig production.