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Losing your nerves? Maybe it's the antibodies

Nature Reviews Immunology volume 9, pages 449–456 (2009)Cite this article

Abstract

We propose that the normal immunocompetent B cell repertoire is replete with B cells making antibodies that recognize brain antigens. Although B cells that are reactive with self antigen are normally silenced during B cell maturation, the blood–brain barrier (BBB) prevents many brain antigens from participating in this process. This enables the generation of a B cell repertoire that is sufficiently diverse to cope with numerous environmental challenges. It requires, however, that the integrity of the BBBs is uninterrupted throughout life to protect the brain from antibodies that crossreact with microorganisms and brain antigens. Under conditions of BBB compromise, and during fetal development, we think that these antibodies can alter brain function in otherwise healthy individuals.

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Figure 1: Antibodies can have a range of effector functions.
Figure 2: Schematic representation of the possible mechanisms regulating the influx and efflux of antibodies through the blood–brain barrier.

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Acknowledgements

We are grateful to O. Bloom, E. Chang, T. Faust, M. Scharff and K. Tracey for suggestions. These studies are supported by grants from the Alliance for Lupus Research and the National Institutes of Health to B.D., P.T.H. and B.T.V.; P.M.-O. is a fellow of the Arthritis Foundation.

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Authors and Affiliations

  1. Betty Diamond, Paola Mina-Osorio and Czeslawa Kowal are at The Feinstein Institute for Medical Research, Center of Autoimmune and Musculoskeletal Diseases, 350 Community Drive, Manhasset, New York 110301, USA.,

    Betty Diamond, Paola Mina-Osorio & Czeslawa Kowal

  2. Department of Neurology and Neuroscience, Patricio T. Huerta and Bruce T. Volpe are at the Weill Medical College of Cornell University, Burke Cornell Medical Research Institute, 785 Mamaroneck Avenue, White Plains, New York 10605, USA.,

    Patricio T. Huerta & Bruce T. Volpe

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Corresponding author

Correspondence to Betty Diamond.

Supplementary information

Supplementary information S1 (table)

Modulators that affect the permeability of the blood-brain (PDF 151 kb)

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FURTHER INFORMATION

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Glossary

Amygdala

An almond-shaped brain region, located deep in the temporal lobe of the brain, which is involved in the neural processing of emotions.

Astrocyte

A star-shaped glial cell that is the most abundant cell type in the brain. Astrocytes regulate the external chemical environment of neurons by removing excess ions, notably potassium, and by recycling neurotransmitter molecules.

Basal ganglia

A group of brain structures (striatum, subthalamic nucleus and substantia nigra) that is located deep in the centre of the brain and is involved in the neural processing of motor function and cognition.

Chorea

Any of several neurological disorders associated with rheumatic fever and marked by involuntary, jerky movements, especially of the arms, legs and face, and by lack of coordination.

Choroid plexus

A vascular extension of the ventricles in the brain that regulates the intraventricular pressure by secreting or absorbing cerebrospinal fluid.

Excitotoxic effect

A pathological process by which neurons are destroyed as a result of excessive levels of the excitatory neurotransmitter glutamate, which overactivates the NMDA receptor and the AMPA receptor, allowing for unusually high levels of calcium to enter the cell and trigger enzymatic cascades that lead to cell death.

Fear-conditioning task

A behavioural method that is used to teach an animal to fear a stimulus that is neutral in nature by associating it with an aversive stimulus (such as a shock, a loud noise or an unpleasant odour).

Glial cell

A non-neuronal cell of the nervous system that is essential for maintaining the health of neurons. According to size, glial cells are divided into microglia and macroglia (astrocytes, oligodendrocytes and others).

Hippocampus

A banana-shaped brain region that is located in the medial temporal lobe of the brain and is involved in the neural processing of memory and spatial navigation.

Leptomeninges

The arachnoid mater and pia mater of the meninges, which is a system of three layers (dura mater, arachnoid mater and pia mater) that encloses the brain.

Limbic encephalitis

An inflammation of the central nervous system in which the pathological signs are localized to the medial temporal lobes.

Microglial cell

A small glial cell that is a specialized type of macrophage. Microglial cells are mobile within the brain, multiply when the brain is damaged and have a protective role.

Neocortex

The outer region of the cerebrum, consisting of superficial grey matter (neurons grouped in several layers) and deeper white matter (myelinated axons). It is essential for the sensory, motor and cognitive organization of behaviour.

Neuromyelitis optica

An autoimmune inflammatory disorder in which the pathological signs are focused on the optic nerves.

Paraneoplastic

A symptom complex that co-occurs with cancer and is mediated by antibodies that recognize antigens in the tumour cells. The antibodies crossreact with antigens in the central nervous system or the peripheral nervous system.

Schwann cell

A glial cell that is filled with myelin and that surrounds the axons of neurons.

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Diamond, B., Huerta, P., Mina-Osorio, P. et al. Losing your nerves? Maybe it's the antibodies. Nat Rev Immunol 9, 449–456 (2009). https://doi.org/10.1038/nri2529

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