B cells and autoantibodies: complex roles in CNS injury

Abstract

Emerging data indicate that traumatic injury to the brain or spinal cord activates B lymphocytes, culminating in the production of antibodies specific for antigens found within and outside the central nervous system (CNS). Here, we summarize what is known about the effects of CNS injury on B cells. We outline the potential mechanisms for CNS trauma-induced B cell activation and discuss the potential consequences of these injury-induced B cell responses. On the basis of recent data, we hypothesize that a subset of autoimmune B cell responses initiated by CNS injury are pathogenic and that targeted inhibition of B cells could improve recovery in cases of brain and spinal cord injury.

Figure 1

Putative mechanisms of B cell activation after traumatic SCI. SCI causes cell death and blood-spinal cord barrier (BSCB) damage (1). At this time, circulating B cells and (pre-formed) immunoglobulins (Igs) cross the BSCB and accumulate at the injury site. BSCB also facilitates drainage of CNS antigens to peripheral lymphoid organs with subsequent B cell recognition of CNS antigens causing B cell proliferation and antibody production (2). Concurrently, APCs present CNS antigens to T cells (3). Cognate interactions between T and B cells amplifies the autoimmune response to CNS antigens such that during the chronic post-injury phase (weeks to months post-SCI), B cells and antibodies continue to accumulate at the injury site forming ectopic follicle-like structures with Igs decorating cells and tissues in and nearby the site of injury.

Figure 2

Autonomic nervous system innervation to the spleen, nerve-associated lymphoid cells (NALC) and adrenal glands. Injuries sustained at different levels of the neuraxis differentially influence immune function. Injuries to the brain or brainstem will block supraspinal control of (dashed arrow) sympathetic preganglionic neurons which in turn regulate noradrenergic postganglionic neurons in the sympathetic chain ganglia. The latter innervate the spleen and adrenal glands. Dysregulation of this “hard-wiring” will adversely affect immune function. Immune function in the periphery and the CNS may also be adversely affected by CNS injury if reflex activation via the vagus nerve is damaged. Normally, this “cholinergic anti-inflammatory vagal reflex” helps limit inflammatory signaling cascades generated in the periphery (see for review).