Clonal expansions of CD4+ B helper T cells in autoimmune myasthenia gravis

Björn Tackenberg, Jens Kruth, Johanna E. Bartholomaeus, Kerstin Schlegel, Wolfgang H. Oertel, Nicholas Willcox, Bernhard Hemmer, Norbert Sommer

Research output: Contribution to journalArticlepeer-review

40 Scopus citations


The weakness in myasthenia gravis (MG) is mediated by T helper cell (Th)-dependent autoantibodies against neuromuscular epitopes. So far, analyzing Th phenotypes or antigen specificities has yielded very few clues to pathogenesis. Here we adopt an alternative antigen-independent approach, analyzing T cell receptor (TCR) Vβ usage/expansions in blood from 118 MG patients. We found major expansions (≥ five standard deviations above the mean of 118 healthy, individually age- and sex-matched controls) in diverse Vβ in 21 patients (17.6%, p<0.001) among CD4+ T cells, and in 45 patients (38.1%, p<0.001) among CD8+ T cells. In informative probands, the expanded CD4+ cells consistently showed a Th cell phenotype (CD57+ CXCR5+) and expressed Th1 cytokines. Furthermore, their expression of markers for activation, lymphocyte trafficking and B cell-activating ability persisted for ≥3 years. Surprisingly, we noted a selective decline in the expansions/their CD57 positivity while the probands' MG was improving. CDR3 spectratyping suggested mono- or oligoclonal origins, which were confirmed by the prevalent TCR Vβ CDR3 sequences of Th cells cloned from repeat bleeds. Thus, our data provide evidence for persistent clonally expanded CD4+ B helper T cell populations in the blood of MG patients. These unexpected CD4+ expansions might hold valuable clues to MG immunopathogenesis.

Original languageEnglish
Pages (from-to)849-863
Number of pages15
JournalEuropean Journal of Immunology
Issue number3
StatePublished - Mar 2007
Externally publishedYes


  • Autoimmunity
  • Myasthenia gravis
  • Oligoclonal
  • T cell receptor


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