B-lymphocyte and plasma cell clonal expansion in monosymptomatic optic neuritis cerebrospinal fluid

Annals of Neurology
Kurt HauboldJeffrey L Bennett

Abstract

The CD19+ B-lymphocyte and CD138+ plasma cell repertoires in cerebrospinal fluid from four patients with monosymptomatic optic neuritis (ON) were analyzed by single-cell reverse transcriptase polymerase chain reaction. Amplified heavy (H)- and light (L)-chain antibody segments were sequenced and used to identify the rearranged germline and J segment of closest homology. Both the B-cell and plasma cell repertoires from ON cerebrospinal fluid demonstrated significant clonal expansion. Up to 75% of the amplified H- and L-chain sequences were contained in overrepresented populations and were somatically mutated, consistent with an antigen-targeted response. The relationship between clonal populations within the CD19+ B lymphocyte and CD138+ plasma cell populations suggests ongoing mutational pressure to refine antigen binding. Our observations demonstrate that an antigen-driven clonal B-lymphocyte and plasma cell response is prominent in the initial stages of central nervous system demyelination and suggest that detection of the disease-relevant antigens in ON may bear on the inciting antigens in chronic inflammatory disorders such as multiple sclerosis.

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Citations

Feb 27, 2008·Folia Microbiologica·P AdamC S Scott
May 10, 2007·Current Neurology and Neuroscience Reports·Molly E Gilbert, Robert C Sergott
Feb 22, 2005·Lancet Neurology·Donald H Gilden
Dec 2, 2011·The Neuroscientist : a Review Journal Bringing Neurobiology, Neurology and Psychiatry·Gregory P OwensJeffrey L Bennett
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Jun 13, 2008·Journal of Neuroimmunology·Jeffrey L BennettGregory P Owens
Nov 13, 2007·Molecular Immunology·Satoru FujimuraNobuo Sakaguchi
Nov 26, 2015·Frontiers in Immunology·Kevin BlauthJeffrey L Bennett
Nov 26, 2009·Annals of Neurology·Jeffrey L BennettBernhard Hemmer
Mar 12, 2015·Journal of the Neurological Sciences·Robert C SergottUNKNOWN ATON Trial Group
Sep 6, 2008·Advances in Immunology·Katherine A McLaughlin, Kai W Wucherpfennig
Sep 29, 2009·Journal of Neuroimmunology·Amer AwadOlaf Stuve
Mar 8, 2007·Expert Review of Neurotherapeutics·Yufen Qin, Stanley van den Noort
May 14, 2005·Current Opinion in Neurology·Alexandre Prat, Jack Antel
Jul 9, 2010·The Journal of Immunology : Official Journal of the American Association of Immunologists·Johanna KöllnYufen Qin
Oct 20, 2007·The Journal of Immunology : Official Journal of the American Association of Immunologists·Gregory P OwensJeffrey L Bennett
Oct 4, 2006·The Journal of Immunology : Official Journal of the American Association of Immunologists·Johanna KollnYufen Qin
Sep 1, 2007·Expert Review of Clinical Immunology·Yufen Qin, Raymond A Sobel

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