IgG Immune Complexes Break Immune Tolerance of Human Microglia.

Marlijn Van Der Poel,Jörg Hamann,Willianne Hoepel,Inge Huitinga,Jeroen Den Dunnen

doi:10.4049/jimmunol.2000130

Abstract

Microglia are phagocytic cells involved in homeostasis of the brain and are key players in the pathogenesis of multiple sclerosis (MS). A hallmark of MS diagnosis is the presence of IgG Abs, which appear as oligoclonal bands in the cerebrospinal fluid. In this study, we demonstrate that myelin obtained post mortem from 8 out of 11 MS brain donors is bound by IgG Abs. Importantly, we show that IgG immune complexes strongly potentiate activation of primary human microglia by breaking their tolerance for microbial stimuli, such as LPS and Poly I:C, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1β. We identified FcγRI and FcγRIIa as the two main responsible IgG receptors for the breaking of immune tolerance of microglia. Combined, these data indicate that IgG immune complexes potentiate inflammation by human microglia, which may play an important role in MS-associated inflammation and the formation of demyelinating lesions.

Highlights

Why The JI? Submit online. Rapid Reviews! 30 days* from submission to initial decision No Triage! Every submission reviewed by practicing scientists Fast Publication! 4 weeks from acceptance to publicatio
We demonstrate that myelin obtained post mortem from 8 out of 11 multiple sclerosis (MS) brain donors is bound by IgG Abs
We investigated whether the myelin of MS brain donors is bound by IgG through an ELISA-based setup, using postmortem myelin isolated from normal-appearing white matter (WM) (NAWM) of MS donors while using nonneurologic donors as controls

Summary

Introduction

We demonstrate that myelin obtained post mortem from 8 out of 11 MS brain donors is bound by IgG Abs. Importantly, we show that IgG immune complexes strongly potentiate activation of primary human microglia by breaking their tolerance for microbial stimuli, such as LPS and Poly I:C, resulting in increased production of key proinflammatory cytokines, such as TNF and IL-1b.

Results

Conclusion