Dynamic changes of the normal B lymphocyte repertoire in CLL in response to ibrutinib or FCR chemo-immunotherapy
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Dynamic changes of the normal B lymphocyte repertoire in CLL in response to ibrutinib or FCR chemo-immunotherapy. / Schliffke, Simon; Sivina, Mariela; Kim, Ekaterina; Wenserski, Lisa von; Thiele, Benjamin; Akyüz, Nuray; Falker-Gieske, Clemens; Statovci, Donjete; Oberle, Anna; Thenhausen, Toni; Krohn-Grimberghe, Artus; Bokemeyer, Carsten; Jain, Nitin; Estrov, Zeev; Ferrajoli, Alessandra; Wierda, William; Keating, Michael; Burger, Jan A.; Binder, Mascha.
in: ONCOIMMUNOLOGY, Jahrgang 7, Nr. 4, 15.01.2018, S. e1417720.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Dynamic changes of the normal B lymphocyte repertoire in CLL in response to ibrutinib or FCR chemo-immunotherapy
AU - Schliffke, Simon
AU - Sivina, Mariela
AU - Kim, Ekaterina
AU - Wenserski, Lisa von
AU - Thiele, Benjamin
AU - Akyüz, Nuray
AU - Falker-Gieske, Clemens
AU - Statovci, Donjete
AU - Oberle, Anna
AU - Thenhausen, Toni
AU - Krohn-Grimberghe, Artus
AU - Bokemeyer, Carsten
AU - Jain, Nitin
AU - Estrov, Zeev
AU - Ferrajoli, Alessandra
AU - Wierda, William
AU - Keating, Michael
AU - Burger, Jan A.
AU - Binder, Mascha
PY - 2018/1/15
Y1 - 2018/1/15
N2 - 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.
AB - 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.
U2 - 10.1080/2162402X.2017.1417720
DO - 10.1080/2162402X.2017.1417720
M3 - SCORING: Journal article
C2 - 29632735
VL - 7
SP - e1417720
JO - ONCOIMMUNOLOGY
JF - ONCOIMMUNOLOGY
SN - 2162-402X
IS - 4
ER -