On 14 thMay 2017, the “Role of the B-Cell Receptor and Other Signaling Pathways in CLL” took place at iwCLL, and was co-chaired by Nicholas Chiorazzi( The Feinstein Institute for Medical Research, Manhasset, NY, USA) and Kostas Stamatopoulos( Center for Research and Technology Hellas, Thessaloniki, Greece).
Hassan Jumaa began the talk by asking is B-Cell Receptor (BCR) expression required for CLL?
Next, it was asked how BCR is activated?
BCRs derived from CLL B-cells are often polyreactive; 3 of 6 tested show polyreactivity. Polyreactivity causes mutual interaction of adjacent BCRs and this interaction can occur in the absence of an exogenous antigen. This kind of BCR activation is cell-autonomous.
Moreover, BCRs from Eµ TCL1 transgenic mice display autonomous signaling. Hassan Jumaa then asked if other lymphoma-derived BCRs also display autonomous signaling? It has been found that BCRs derived from MM, MCL, MZL, and FL do not display autonomous signaling.
However, as mentioned above, not all CLL-derived BCRs are polyreactive. Only 25% (1/4) tested BCRs from Eµ TCL1 transgenic mice display polyreactivity.
The Heavy Chain Complementarity-Determining Region 3 (HCDR3), which is known to play a key role in the binding of monoreactive antibodies to antigens, has been found to interact with intrinsic BCR structures. Different HCDR3 have different interaction partners. The limited amount of BCR-intrinsic structures might explain the restricted repertoire and the stereotypes of HCDR3 regions in CLL ( Dühren-von Minden et al.2012).