Figure 1.

Potential patterns of B cell trafficking in multiple sclerosis. (A) The predominant stream of migratory B cells from the periphery to the CNS are likely to consist of either memory B cells or plasmablasts produced in the germinal centers of cervical lymph nodes. The presence of CSF B cell clones closely related to germline sequences suggests that naïve B cells may transit the blood–brain barrier to populate meningeal germinal center-like structures and produce CNS-restricted memory B cells. (B) Both migratory plasmablasts and memory B cells may contribute to the pool of central nervous system (CNS) antibody-secreting cells that produce the oligoclonal bands. Memory B cells may also enter germinal centers in meningeal lymphoid aggregates or draining cervical lymph nodes, resulting in further clonal expansion and affinity maturation. (C) A significant fraction of expanded B cell clones circulates between CNS compartments: cerebrospinal fluid, meningeal lymphoid aggregates, parenchymal lesions, and normal white matter. Solid arrows represent established pathways; dashed arrows represent putative pathways.