Dynamic changes of the normal B lymphocyte repertoire in CLL in response to ibrutinib or FCR chemo-immunotherapy

  • Simon Schliffke
  • Mariela Sivina
  • Ekaterina Kim
  • Lisa von Wenserski
  • Benjamin Thiele
  • Nuray Akyüz
  • Clemens Falker-Gieske
  • Donjete Statovci
  • Anna Oberle
  • Toni Thenhausen
  • Artus Krohn-Grimberghe
  • Carsten Bokemeyer
  • Nitin Jain
  • Zeev Estrov
  • Alessandra Ferrajoli
  • William Wierda
  • Michael Keating
  • Jan A. Burger
  • Mascha Binder

Beteiligte Einrichtungen

Abstract

Using next-generation immunoglobulin (IGH) sequencing and flow cytometry, we characterized the composition, diversity and dynamics of non-malignant B cells in patients undergoing treatment with the Bruton tyrosine kinase (BTK) inhibitor ibrutinib or chemo-immunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR). During ibrutinib therapy, non-malignant B cell numbers declined, but patients maintained stable IGH diversity and constant fractions of IGH-mutated B cells. This indicates partial preservation of antigen-experienced B cells during ibrutinib therapy, but impaired replenishment of the normal B cell pool with naïve B cells. In contrast, after FCR we noted a recovery of normal B cells with a marked predominance of B cells with unmutated IGH. This pattern is compatible with a deletion of pre-existing antigen-experienced B cells followed by repertoire renewal with antigen-naïve B cells. These opposite patterns in B cell dynamics may result in different responses towards neoantigens versus recall antigens, which need to be further defined.

Bibliografische Daten

OriginalspracheEnglisch
ISSN2162-4011
DOIs
StatusVeröffentlicht - 15.01.2018