Heterogeneity of B cells in the immunoregulatory niche at the cribriform plate during EAE

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Presentation Time: 11:30 AM - 12:45 PM
Poster Board Number: B603
Abstract ID: 5598

Presenting Author:
Kristof G Kovacs , Research Associate at Univ. of Wisconsin, Madison

Abstract:

B cells may play regulatory roles in multiple sclerosis (MS) patients and experimental autoimmune encephalomyelitis (EAE) mice. Recently, B cell development was revealed to occur in the meninges, inducing B cell tolerance toward central nervous system (CNS) antigens. Our group recently showed that neuroinflammation in EAE induces an immune regulatory niche at the cribriform plate (CP) meningeal lymphatics. Here we characterize the phenotype and regulatory function of B cells at the CP in a mouse model of CNS autoimmunity.

Using immunohistochemistry and cytofluorimetry, we found that the number of B cells increases during EAE at the CP niche. The majority of B cells form doublets, triplets and larger aggregates with dendritic cells (DC) at the CP. Single-cell RNA-sequencing of DC-interactor B cells showed that B cells undergo maturation at the CP. We identified upregulated genes indicative of different maturation stages characteristic of common lymphoid progenitors (Ly6D), early pro-B cells (Vpreb3, FOXO1), immature (BAFF-R) and mature (CD20) B cells. MetaScape analysis confirmed that B cells differentiate and become activated at the CP. We hypothesize that interaction with B cells induces a tolerogenic state in DCs, promoting the B cell-driven regulation of CNS autoimmunity.

In conclusion, we propose that B cells contribute to the formation of the CP immunoregulatory niche. This holds promise in elucidating potential implications of B cell immunomodulatory therapies in MS.