Autoantigen induced clonal expansion in immortalized B cells from the peripheral blood of multiple sclerosis patients

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• 作者：Judith Fraussen ; Kathleen Vrolix ; Nele Claes ; Pilar Martinez-Martinez ; Mario Losen ; Raymond Hupperts ; Bart Van Wijmeersch ; Mercedes Espi?o ; Luisa M. Villar ; Marc H. De Baets ; Piet Stinissen ; Veerle Somers
• 关键词：Multiple sclerosis ; Clinically isolated syndrome ; B cell immortalization ; Complementarity determining region 3 ; Clonal B cell expansion ; Autoreactivity
• 刊名：Journal of Neuroimmunology
• 出版年：2013
• 出版时间：15 August, 2013
• 年：2013
• 卷：261
• 期：1-2
• 页码：98-107
• 全文大小：860 K

文摘

We studied Ig heavy chain (VDJ) sequences and antigen reactivity of 412 immortalized B cell lines from the peripheral blood of 10 multiple sclerosis (MS) patients, 4 clinically isolated syndrome (CIS) patients and 6 healthy controls (HCs). 78/238 (32.8 % ) MS and CIS B cell lines were part of 9 clonally expanded B cell populations, of which 5 were present in multiple patients. Increased VH1 gene family usage was evidenced for MS B cells, with 29.2 % expressing VH1-69. Affinity maturation in MS and CIS was indicated by increased Ig VDJ mutations. Autoantibody producing B cells reactive to intracellular antigens were significantly higher in MS (25 % ) and CIS (28 % ) patients than in HCs (5 % ), including 3/9 expanded B cell clones. Specificity for phosphatidylcholine was observed for 1/9 B cell clones. These findings indicate clonally expanded autoreactive B cells with affinity maturation in the peripheral blood in MS and CIS.