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 use...
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| Veröffentlicht in: | Annals of neurology 2004-07, Vol.56 (1), p.97-107 |
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| container_title | Annals of neurology |
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| creator | Haubold, Kurt Owens, Gregory P. Kaur, Paramjit Ritchie, Alanna M. Gilden, Donald H. Bennett, Jeffrey L. |
| description | 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. Ann Neurol 2004;56:97–107 |
| doi_str_mv | 10.1002/ana.20152 |
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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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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. Ann Neurol 2004;56:97–107</description><subject>Amino Acid Sequence</subject><subject>Antigens, CD19 - genetics</subject><subject>Antigens, CD19 - immunology</subject><subject>B-Lymphocytes - immunology</subject><subject>Base Sequence</subject><subject>Biological and medical sciences</subject><subject>Cell Separation</subject><subject>Complementarity Determining Regions - genetics</subject><subject>Flow Cytometry</subject><subject>Humans</subject><subject>Immune System - physiology</subject><subject>Immunoglobulin Heavy Chains - genetics</subject><subject>Immunoglobulin Heavy Chains - immunology</subject><subject>Immunoglobulin Light Chains - genetics</subject><subject>Immunoglobulin Light Chains - immunology</subject><subject>Immunoglobulin Variable Region - genetics</subject><subject>Immunoglobulin Variable Region - metabolism</subject><subject>Lymphocyte Activation</subject><subject>Medical sciences</subject><subject>Membrane Glycoproteins - genetics</subject><subject>Membrane Glycoproteins - immunology</subject><subject>Molecular Sequence Data</subject><subject>Neurology</subject><subject>Optic Neuritis - cerebrospinal fluid</subject><subject>Optic Neuritis - immunology</subject><subject>Plasma Cells - immunology</subject><subject>Proteoglycans - genetics</subject><subject>Proteoglycans - immunology</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Syndecan-1</subject><subject>Syndecans</subject><issn>0364-5134</issn><issn>1531-8249</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkM1u1DAUhS1ERYeBBS-AsqESi7T-iZ14OVSloFalSKBKbKw7ji0Mjh3sRHTeHocZfjaIje_C37lX50PoGcGnBGN6BgFOKSacPkArwhmpO9rIh2iFmWhqTlhzjB7n_AVjLAXBj9BxQcsXFiukX9V-N4yfo95NpoLQV6OHPECljfeV9jGAr8z9CCG7GCoXqiGGmEtkigNMTldxXN5g5uQml0sumW2KeXRL0vrZ9U_QkQWfzdPDXKOPry8-nL-pr99dvj3fXNe6oZjWcts0XEjaMYmFpYQw04LlXYtZK7Shghm5FQK4xrTTnHa91Z2VPddWY00ZW6OT_d4xxW-zyZMaXF56QDBxzkoI0TJO6X9BIiWjtIhbo5d7UJdGORmrxuQGSDtFsFrUq6Je_VRf2OeHpfN2MP0f8uC6AC8OAGQN3iYI2uW_OEk6IpYaZ3vuu_Nm9--LanOz-XW63idcnsz97wSkr6o0brm6u7lU5NNVd_te3Klb9gMO8Knj</recordid><startdate>200407</startdate><enddate>200407</enddate><creator>Haubold, Kurt</creator><creator>Owens, Gregory P.</creator><creator>Kaur, Paramjit</creator><creator>Ritchie, Alanna M.</creator><creator>Gilden, Donald H.</creator><creator>Bennett, Jeffrey L.</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Willey-Liss</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7T5</scope><scope>7TK</scope><scope>H94</scope><scope>7X8</scope></search><sort><creationdate>200407</creationdate><title>B-lymphocyte and plasma cell clonal expansion in monosymptomatic optic neuritis cerebrospinal fluid</title><author>Haubold, Kurt ; 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| subjects | Amino Acid Sequence Antigens, CD19 - genetics Antigens, CD19 - immunology B-Lymphocytes - immunology Base Sequence Biological and medical sciences Cell Separation Complementarity Determining Regions - genetics Flow Cytometry Humans Immune System - physiology Immunoglobulin Heavy Chains - genetics Immunoglobulin Heavy Chains - immunology Immunoglobulin Light Chains - genetics Immunoglobulin Light Chains - immunology Immunoglobulin Variable Region - genetics Immunoglobulin Variable Region - metabolism Lymphocyte Activation Medical sciences Membrane Glycoproteins - genetics Membrane Glycoproteins - immunology Molecular Sequence Data Neurology Optic Neuritis - cerebrospinal fluid Optic Neuritis - immunology Plasma Cells - immunology Proteoglycans - genetics Proteoglycans - immunology Reverse Transcriptase Polymerase Chain Reaction Syndecan-1 Syndecans |
| title | B-lymphocyte and plasma cell clonal expansion in monosymptomatic optic neuritis cerebrospinal fluid |
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