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Next-generation sequencing (NGS) may be a useful tool to determine how B cells migrate and mature across the blood-brain barrier of multiple sclerosis (MS), and it may be possible to better understand the pathophysiological mechanisms involved in neuroinflammation.

According to a systemic study, using next-generation sequencing (NGS) to help researchers outline the migration pattern and maturation of B cells in multiple sclerosis (MS), which indicates that B cells have passed through the blood-brain barrier (BBB). Strong exchange. Review.

The results of the review published in the journal Diagnosis indicate that B cells passing through the BBB at such a high speed may contribute to the autoimmune circuit, and the further development of sequencing technology may help accurately decipher the pathophysiological mechanism of B cells. Neuroinflammation.

"The development of high-throughput next-generation sequencing has further promoted the development of B-cell immunology and helped to representatively evaluate the peripheral blood B-cell pool... so as to gain insights into the maturation process of B-cells and the mode of transport across the blood-brain barrier. ," the investigator wrote.

B cells are essential to the adaptive immune system and play a key role in the pathogenesis of several neuroinflammatory diseases. Central nervous system (CNS) inflammation can be regulated or triggered by B cells. B cells can enter the central nervous system through the BBB, blood-cerebrospinal fluid (CSF) or the surface barrier of the brain.

During neuroinflammation, B cells can be found in CSF in infectious and autoimmune diseases (including MS). Studies have shown that the coordinated response between T cells and B cells can cause inflammation of the central nervous system, leading to demyelination and neuronal damage. Although the level of B cells in CSK in MS patients is relatively high, there is still no clear CSK antibody antigen target, and it has not been consistently identified in MS.

Researchers conducted a database search of published reports and articles published as of May 2021. To be included, these studies must include human research data, have not reported previously published data, and must account for the sequencing of B cell receptors. Of the 135 identified papers, 38 were selected for analysis.

In addition, it has been suggested that B cells in the cerebrospinal fluid may recirculate in the peripheral blood and may drain through the cervical lymph nodes, where they interact with other immune cells and may undergo further maturation and interaction.

The researchers said that the most striking result they found is that there is a strong exchange of B cell trafficking between BBBs, which suggests that other compartments outside the CNS are involved in B cell migration.

The analysis results show that, due to the recombination, affinity maturation, class-switching recombination and somatic hypermutation of VDJ fragments, the B cell receptor has a high degree of variability. Therefore, B-cell immunoglobulin transcripts containing the same fragment and a highly similar somatic hypermutation profile are considered to be clonally related.

The application of NGS can perform representative sequencing of CSF and peripheral blood B cell banks, which can check the B cell trafficking in the BBB. Some studies have shown that there is a large clonal overlap between peripheral blood and cerebrospinal fluid B cells. The researchers said that their analysis provided evidence that B cells can freely migrate across the tissue barrier, and that a large number of B cells mature outside the CNS.

In addition, studies have shown that the CSF transcriptome and proteome B cell pools show that intrathecal immunoglobulin (Ig) is produced by CSF B cells and B cell clones. Intrathecal Ig synthesis is related to the severity and progression of MS disease.

Researchers say that NGS can be a powerful tool for studying B cell transport and maturation between different compartments, and help understand the pathology associated with B cells in the CNS.

Ruschil C, Kemmerer CL, Beller L, Baretnet G, Kowarik MC. Next generation sequencing of cerebrospinal fluid B cell bank in multiple sclerosis and other neuroinflammatory diseases-a comprehensive review. diagnosis. Published online on October 11, 2021. doi:10.3390/diagnostics11101871