Postdoc Visiting Fellow National Institutes of Health Bethesda, Maryland, United States
Disclosure(s):
Nagela Ghabdan Zanluqui, PhD: No financial relationships to disclose
Introduction/Rationale: Immune cells within the meninges are increasingly recognized as key regulators of CNS homeostasis and disease. The dura mater, which contains diverse innate and adaptive immune populations, also supports B cell development. We recently identified organized lymphoid architecture surrounding a fenestrated venous plexus at the rostral–rhinal confluence of sinuses, termed the rostral-rhinal venolymphatic hub (hub). Following intranasal viral infection, this hub mounts robust germinal center (GC) responses composed of T follicular helper (Tfh) cells and GC B cells undergoing proliferation, class-switch recombination, and somatic hypermutation. Here we evaluate the role of the hub in the development of autoimmunity.
Methods: Using complementary structural and functional approaches as molecular biology, imaging and flow cytometric analysis.
Results: We show that this same hub also supports autoimmune responses to CNS antigens, particularly myelin debris that preferentially accumulates at this site. This deposition appears to result from a loose glial limitans over the olfactory bulbs and the proximity of fenestrated vasculature that drains into the hub. B cells act as key “housekeepers,” as their depletion markedly increases myelin accumulation. Beyond debris clearance, hub-resident B cells express PDL-1 and TGFβ, suggesting a regulatory program that may reinforce tolerance to self-antigens. During autoimmune priming, myelin oligodendrocyte glycoprotein (MOG)–reactive CD4⁺ T cells preferentially localize to the hub, engage B cells, proliferate, and differentiate into Tfh cells. B cell depletion augments the accumulation of these autoreactive T cells in the hub and accelerates onset of EAE.
Conclusion: Collectively, these findings reveal how dural lymphoid architecture positioned around a specialized vascular plexus can sample foreign and self-antigens, generating responses that either protect against infection or drive autoimmune pathology in the adjacent CNS.
