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J Neuroimmunol. 2017 Aug 15;309:88-99. doi: 10.1016/j.jneuroim.2017.05.004. Epub 2017 May 17.

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

Author information

1
Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Microbiology, Immunology and Biochemistry, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: rlisak@med.wayne.edu.
2
Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: lnedelk@med.wayne.edu.
3
Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA; Department of Microbiology, Immunology and Biochemistry, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: jbenjami@med.wayne.edu.
4
Department of Oncology, Wayne State University School of Medicine and Karmanos Cancer Institute, Detroit, MI, USA. Electronic address: DLS2DA@hscmail.mcc.virginia.edu.
5
Department of Neurology, Wayne State University School of Medicine, Detroit, MI, USA. Electronic address: bbealmea@med.wayne.edu.
6
Department of Neurology, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada; Department of Neurology and Center for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: hanane.touil@mail.med.upenn.edu.
7
Department of Neurology, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada; Department of Neurology and Center for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: rui.li@mail.med.upenn.edu.
8
Department of Neurology, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada. Electronic address: g.muirhead@gmail.com.
9
Department of Neurology, McGill University, Montreal Neurological Institute, Montreal, Quebec, Canada; Department of Neurology and Center for Neuroinflammation and Neurotherapeutics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Electronic address: amitbar@upenn.edu.

Abstract

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 >300kDa. B cells could contribute to damage within the central nervous system by secreting molecules toxic to OL and neurons.

KEYWORDS:

B cells; Cell death; Cytokines; Multiple sclerosis; Neurons; Oligodendrocytes

PMID:
28601295
DOI:
10.1016/j.jneuroim.2017.05.004
[Indexed for MEDLINE]

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