Figure 1. B cells lineage from bone marrow to CNS.

B-cells originating in the bone marrow exit toward the blood stream as immature B-cells; they enter the SLO and specialize in the germinal centers producing memory B cells and plasmablasts, which in pathologic conditions, are able to gain access to the CNS. The TLO is formed in the meninges during chronic inflammation in the deep brain cortical sulci and share organogenesis with the SLO ²⁴. Podoplanin and the Th17 signature cytokine IL-17 have been associated with ectopic lymphoneogenesis in human diseases whereas BAFF is a key factor for mutation and survival of B cells which is produced by astrocytes in the CNS ^{3, 25}. BAFF: B-cell activating factor of the tumor necrosis factor family; Balt: bronchial associated lymphoid tissue; CCL19: chemokine (c-c motif) ligand 19; CSF: cerebrospinal fluid; CXCL13: chemokine (C-X-C motif) ligand 13; FDC: follicular dendritic cells; GC: germinal center; LT: lymphotoxin α1β2/LTβR system; LLPC: long lived plasma cells; MS: multiple sclerosis; PC: plasma cell; SLO: secondary lymphoid organ; TLO: tertiary lymphoid organ.