CNS Aquaporin-4-specific B cells connect with multiple B-cell compartments in neuromyelitis optica spectrum disorder

Autor:	Hannah Schumann, Bernhard Hemmer, Gregory P. Owens, Markus C. Kowarik, Christiane Gasperi, Alanna M. Ritchie, Scott Wemlinger, Monika Dzieciatkowska, Jeffrey Bennett, David P. Astling
Rok vydání:	2017
Předmět:	0301 basic medicine Population Immunoglobulin light chain Transcriptome 03 medical and health sciences 0302 clinical medicine Cerebrospinal fluid medicine education Research Articles B cell education.field_of_study Neuromyelitis optica biology General Neuroscience medicine.disease 3. Good health 030104 developmental biology medicine.anatomical_structure Aquaporin 4 Immunology biology.protein Neurology (clinical) Antibody 030217 neurology & neurosurgery Research Article
Zdroj:	Annals of Clinical and Translational Neurology
ISSN:	2328-9503
Popis:	Objectives Neuromyelitis optica spectrum disorder (NMOSD) is a severe inflammatory disorder of the central nervous system (CNS) targeted against aquaporin-4 (AQP4). The origin and trafficking of AQP4-specific B cells in NMOSD remains unknown. Methods Peripheral (n = 7) and splenic B cells (n = 1) recovered from seven NMOSD patients were sorted into plasmablasts, naive, memory, and CD27-IgD- double negative (DN) B cells, and variable heavy chain (VH) transcriptome sequences were generated by deep sequencing. Peripheral blood (PB) VH repertoires were compared to the same patient's single-cell cerebrospinal fluid (CSF) plasmablast (PB) VH transcriptome, CSF immunoglobulin (Ig) proteome, and serum Ig proteome. Recombinant antibodies were generated from paired CSF heavy- and light chains and tested for AQP4 reactivity. Results Approximately 9% of the CSF VH sequences aligned with PB memory B cells, DN B cells, and plasmablast VH sequences. AQP4-specific VH sequences were observed in each peripheral B-cell compartment. Lineage analysis of clonally related VH sequences indicates that CSF AQP4-specific B cells are closely related to an expanded population of DN B cells that may undergo antigen-specific B-cell maturation within the CNS. CSF and serum Ig proteomes overlapped with the VH sequences from each B-cell compartment; the majority of matches occurring between the PB VH sequences and serum Ig proteome. Interpretation During an acute NMOSD relapse, a dynamic exchange of B cells occurs between the periphery and CNS with AQP4-specific CSF B cells emerging from postgerminal center memory B cells and plasmablasts. Expansion of the PB DN B-cell compartment may be a potential biomarker of NMOSD activity.
Databáze:	OpenAIRE
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