B Cell Repertoire Expansion Occurs in Meningeal Ectopic Lymphoid Tissue

Overview

Journal JCI Insight

Specialties Biomedical Engineering
General Medicine

Date 2016 Dec 13

PMID 27942581

Citations 37

Authors

Klaus Lehmann-Horn

Sheng-Zhi Wang

Sharon A Sagan

Scott S Zamvil

H-Christian von Budingen

Affiliations

Soon will be listed here.

Abstract

Ectopic lymphoid tissues (ELT) can be found in multiple sclerosis (MS) and other organ-specific inflammatory conditions. Whether ELT in the meninges of central nervous system (CNS) autoimmune disease exhibit local germinal center (GC) activity remains unknown. In an experimental autoimmune encephalomyelitis model of CNS autoimmunity, we found activation-induced cytidine deaminase, a GC-defining enzyme, in meningeal ELT (mELT) densely populated by B and T cells. To determine GC activity in mELT, we excised meningeal lymphoid aggregates using laser capture microscopy and evaluated B cell repertoires in mELT and secondary lymphoid organs by next-generation immune repertoire sequencing. We found immunoglobulin heavy chain variable region sequences that were unique to mELT and had accumulated functionally relevant somatic mutations, together indicating localized antigen-driven affinity maturation. Our results suggest that B cells in mELT actively participate in CNS autoimmunity, which may be relevant to mELT in MS and ELT in other chronic inflammatory conditions.

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