B cells from patients with multiple sclerosis induce cell death via apoptosis in neurons in vitro

•Secreted factors from cultured B cells from relapsing remitting MS (RRMS) patients, but not normal controls (NC), are cytotoxic to rat and human neurons.•Cytotoxicity is independent of Ig and multiple cytokines, not complement-mediated, and occurs partially by apoptosis.•The factor/s are > 300 kDa.•CNS-compartmentalized B cells (such as meningeal B cells) could mediate subpial demyelination and neuronal/axonal damage by secreting one or more non-immunoglobulin factors, compatible with cortical lesion immunopathology.

B cells mediate multiple sclerosis (MS) pathogenesis by mechanisms unrelated to immunoglobulin (Ig). We reported that supernatants (Sup) from cultured B cells from blood of relapsing remitting MS (RRMS) patients, but not normal controls (NC), were cytotoxic to rat oligodendrocytes (OL). We now show that RRMS blood B cells, not stimulated in vitro, secrete factor/s toxic to rat and human neurons. Cytotoxicity is independent of Ig and multiple cytokines, not complement-mediated, and involves apoptosis. The factor/s have an apparent mw of > 300 kDa. B cells could contribute to damage within the central nervous system by secreting molecules toxic to OL and neurons.

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