Introduction Previous studies have documented that humoral immune responses participated in neurological damage in neurosyphilis patients. However, the mechanisms that trigger and maintain humoral immunity involved in neurosyphilis remain unknown.

Methods Using flow cytometry expression of B cells was measured in neurosyphilis and non-neurosyphilis. Expression of immunoglobulin indices and CXCL13 was detected by ELISA. A modified chamber assays were used to migration and inhibition assays. The presence of CXCL13⁺cells, CD20⁺B cells, CD3⁺T cells, CD138⁺plasma cells and CD35⁺follicular dendritic cells was studied by immunohistochemistry.

Results We found that enrichment of B cells were observed and activated in the cerebrospinal fluid (CSF) of NS patients. Immunoglobulin indices were increased and associated with the progress to neurosyphilis. Moreover, high expression of CSF CXCL13 mediated B cells migration both in vitro and in vivo. More importantly, there was a positive correlation between the CSF B cells, immunoglobulin indices, and CSF CXCL13 levels. Interestingly, ectopic germinal centres (EGCs), the important structures for the maintenance of humoral immunity, were observed in the intracranial syphilitic gumma.

Conclusion CXCL13/CXCR5 mediated the aggregation of B cells, which directed the aberrant humoral immune responses via the formation of EGCs. Our observations suggest a molecular mechanism of neurological damage in neurosyphilis.