B cell repertoire expansion occurs in meningeal ectopic lymphoid tissue
Klaus Lehmann-Horn, Sheng-zhi Wang, Sharon A. Sagan, Scott S. Zamvil, H.-Christian von Büdingen
Klaus Lehmann-Horn, Sheng-zhi Wang, Sharon A. Sagan, Scott S. Zamvil, H.-Christian von Büdingen
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Research Article

B cell repertoire expansion occurs in meningeal ectopic lymphoid tissue

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.

Authors

Klaus Lehmann-Horn, Sheng-zhi Wang, Sharon A. Sagan, Scott S. Zamvil, H.-Christian von Büdingen

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Figure 3

mELT and SLO each have their private Ig repertoires with relatively small overlap between each other.

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mELT and SLO each have their private Ig repertoires with relatively smal...
(A) Venn diagrams representing the number of unique IgG heavy chain sequences (comparing 2 compartments per diagram) that were found either exclusively in one compartment or in both compartments (overlap). The size of each circle is proportional to the count it represents. (B) Bar graphs representing the percentage (%) of overlapping unique sequences between 2 compartments of all unique sequences in the designated reference compartment (in bold in the x-axis label) are shown. Mean of 5 Th×2D2 EAE mice is shown (error bars, SEM). Differences between groups were not significant (Friedman test with Dunn’s multiple comparisons test). (C) Venn diagram representing the number of unique IgG heavy chain sequences in various immune compartments (blood, LN, spleen, and 2 spatially independent spinal cord mELT) and their overlap in all possible combinations. (A and C) Data from one Th×2D2 EAE mouse (representative of 5) are shown. (A–C) The entire region starting with the first nucleotide of the CDR1 and extending to the last nucleotide of the CDR3 is included. mELT, meningeal ectopic lymphoid tissue; SLO, secondary lymphoid organ; EAE, experimental autoimmune encephalomyelitis; LN, lymph node; CDR, complementarity determining region.