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

Judith Fraussen, Kathleen Vrolix, Nele Claes, Pilar Martinez-Martinez, Mario Losen, Raymond Hupperts, Bart Van Wijmeersch, Mercedes Espino, Luisa M. Villar, Marc H. De Baets, Piet Stinissen, Veerle Somers*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

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.
Original languageEnglish
Pages (from-to)98-107
JournalJournal of Neuroimmunology
Volume261
Issue number1-2
DOIs
Publication statusPublished - 15 Aug 2013

Keywords

  • Multiple sclerosis
  • Clinically isolated syndrome
  • B cell immortalization
  • Complementarity determining region 3
  • Clonal B cell expansion
  • Autoreactivity

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