B-lymphocyte and plasma cell clonal expansion in monosymptomatic optic neuritis cerebrospinal fluid.
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.
Haubold
Kurt
K
Department of Neurology, University of Colorado Health Sciences Center, Denver, CO 80262, USA.
Owens
Gregory P
GP
Kaur
Paramjit
P
Ritchie
Alanna M
AM
Gilden
Donald H
DH
Bennett
Jeffrey L
JL
D000595:Amino Acid Sequence; D018941:Antigens, CD19 / Q000235:genetics / Q000276:immunology*; D001402:B-Lymphocytes / Q000276:immunology*; D001483:Base Sequence; D002469:Cell Separation; D022801:Complementarity Determining Regions / Q000235:genetics; D005434:Flow Cytometry; D006801:Humans; D007107:Immune System / Q000502:physiology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D007147:Immunoglobulin Light Chains / Q000235:genetics / Q000276:immunology; D007135:Immunoglobulin Variable Region / Q000235:genetics / Q000378:metabolism; D008213:Lymphocyte Activation; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology*; D008969:Molecular Sequence Data; D009902:Optic Neuritis / Q000134:cerebrospinal fluid* / Q000276:immunology*; D010950:Plasma Cells / Q000276:immunology*; D011509:Proteoglycans / Q000235:genetics / Q000276:immunology*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D053668:Syndecan-1; D053667:Syndecans
D018941:Antigens, CD19; D022801:Complementarity Determining Regions; D007143:Immunoglobulin Heavy Chains; D007147:Immunoglobulin Light Chains; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; D011509:Proteoglycans; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans