IRTG 1054 Lecture - Elias Hobeika

Title: B cell antigen receptor signaling in maintenance of mature as well as CLL-like B cells

Expression of a functional B cell antigen receptor (BCR) is essential for the maintenance and differentiation of B cells. It is thus not surprising that multiple B cell-derived malignancies critically depend on BCR-signaling in terms of their development and retention. Accordingly, in chronic lymphocytic leukemia (CLL) inhibition of signaling molecules downstream of the BCR, like the Bruton’s Tyrosine Kinase (BTK) by Ibrutinib, leads to the efficient eradication of the malignant cells.

In the presented work, we investigate the importance of the BCR signaling for the maintenance of leukemic B cells derived from the EmTcl-1 mouse model for a CLL-like disease. We employ tamoxifen-inducible Cre-recombinase expressed from the Iga-encoding mb‑1 locus (mb1‑CreERT2) to switch off the expression of signal-transducing BCR-components Igα or Igβ.

The assessment of leukemic cells in the mb1-CreERT2 mouse line was possible due to the high recombination efficiency of the mb1 or B29 loci, encoding Igα or Igβ respectively. Inactivation of either Igα or Igβ on the EmTcl-1-transgenic background resulted in a rapid demise of the CLL-like B cells. Taken together our results reveal that BCR-expression and subsequently BCR-signaling are indispensable for the maintenance of CLL-like B cells in vivo. At the moment, we are investigating the signaling pathways, which may contribute to the rescue of the BCR-deficient CLL-like B cells from elimination. To our knowledge, this is the first genetic evidence that CLL-like B cells critically depend on BCR-signaling for their survival.

Elias Hobeika - Website

 

Host: Madlen Steinert (PhD student in Ludger Klein's lab)

 

Venue:

BioMedical Center (BMC), Room N 02.017,
Großhaderner Str. 9, Planegg-Martinsried

If you wish to talk to the speaker, please contact Katharina Frank