Next Generation Sequencing of Cerebrospinal Fluid B Cell Repertoires in Multiple Sclerosis and Other Neuro-Inflammatory Diseases-A Comprehensive Review.

Christoph Ruschil,Lena Beller,Markus Christian Kowarik,Constanze Louisa Kemmerer,Gisela Gabernet

doi:10.3390/diagnostics11101871

Abstract

During the last few decades, the role of B cells has been well established and redefined in neuro-inflammatory diseases, including multiple sclerosis and autoantibody-associated diseases. In particular, B cell maturation and trafficking across the blood–brain barrier (BBB) has recently been deciphered with the development of next-generation sequencing (NGS) approaches, which allow the assessment of representative cerebrospinal fluid (CSF) and peripheral blood B cell repertoires. In this review, we perform literature research focusing on NGS studies that allow further insights into B cell pathophysiology during neuro-inflammation. Besides the analysis of CSF B cells, the paralleled assessment of peripheral blood B cell repertoire provides deep insights into not only the CSF compartment, but also in B cell trafficking patterns across the BBB. In multiple sclerosis, CSF-specific B cell maturation, in combination with a bidirectional exchange of B cells across the BBB, is consistently detectable. These data suggest that B cells most likely encounter antigen(s) within the CSF and migrate across the BBB, with further maturation also taking place in the periphery. Autoantibody-mediated diseases, such as neuromyelitis optica spectrum disorder and LGI1 / NMDAR encephalitis, also show features of a CSF-specific B cell maturation and clonal connectivity with peripheral blood. In conclusion, these data suggest an intense exchange of B cells across the BBB, possibly feeding autoimmune circuits. Further developments in sequencing technologies will help to dissect the exact pathophysiologic mechanisms of B cells during neuro-inflammation.

Highlights

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Studies in MS with conventional B cell repertoire sequencing in the cerebrospinal fluid (CSF) compartment were included conventional B cell repertoire sequencing in the CSF compartment were included in in the analysis, in order to compare between the different methods and complete the the analysis, in order to compare between the different methods and complete the picture picture of B cell pathophysiology in MS
Bcell repertoire sequencing in complex datasets; for this reason we ordered themass results accordingresults to findings from basic datasets; for this reason we ordered the results according to findings from basicacross repertoire repertoire analysis, clonal expansion within the CSF, Bcell trafficking the blood–brain barrier (BBB)

Summary

Introduction

Neuro-Inflammatory Diseases—Cerebrospinal Fluid (CSF) Findings, Including Routine. Bcells are an essential part of the adaptive immune system and play important roles in the pathogenesis of several neuro-inflammatory diseases. The functional properties of B cells are manifold and include antigen recognition through B cell receptors (BCR). Specific antibody production, and antigen presentation to other immune cells and the secretion of cytokines [1]. Central nervous system (CNS) inflammation is often modulated or even initiated by B cells. The priming of these B cells can either occur in the peripheral compartment, followed by trafficking into the CNS, or by a compartmentalized. There are several pathways by which B cells could enter the CNS, including the blood–brain barrier (BBB), blood–cerebrospinal fluid (CSF)

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