B cells in multiple sclerosis

Figures & data

Box 1. B cell functions in autoimmune disease.

• Secretion of pathogenic autoantibodies

• Mechanisms:

▪ Complement-dependent destruction of target cells

▪ Blockade of surface structures (e.g. direct blindfolding or internalization of receptors)

▪ Autoantigen complex binding to antigen presenting cells

• Evidence:

▪ Neuromyelitis optica (NMO, alias Devic’s disease); anti-aquaporin-4 autoantibodies)

▪ Autoimmune encephalitis variants: anti-neuronal receptor autoantibodies (N-methyl-D-aspartic acid [NMDA], α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid [AMPA], gamma-aminobutyric acid [GABA], etc.)

• MS: no pathogenic autoantibodies as yet

• Antigen presentation

• Mechanism: soluble autoantigens bound to B cell surface immunoglobulin (specific autoantibody), concentrated and processed for presentation to autoimmune T cells

• Evidence: spontaneous EAE model (OSE mouse), in vitro antigen presentation

• MS: CD40/IL-4 activated B-APC present antigen to CD4^+ T cells (no preferential preference shown)

• Cytokine release

• Mechanisms: B-cell derived cytokines/chemokines imprint the local immune milieu

▪ B-regs: release anti-inflammatory cytokines (IL-10, TGF-b);

▪ Pro-inflammatory B cells: release cytokines like GM-CSF to fuel inflammatory (auto-)immune responses

• Evidence: isolation from recovering EAE mice, transfer of protection;

• MS: isolation of CD4^+ memory subsets from peripheral blood lymphocytes

• Autoantigen transport

• Mechanism: antigen specific B cells capture antigen via surface antigen receptors and transport them to splenic and/or lymph node follicles

• Evidence: experimental systems;

• MS: not known

Figure 1. Recruitment of MOG autoimmune B cells in the CNS draining cervical lymph nodes. B cell recruitment depends on activated MOG specific helper T cells entering via blood or lymphatic vessels, as well as on MOG containing material transported from the brain via lymph vessels (soluble, particulate or by phagocytes).