How the immune system generates a vast antibody repertoire to fight infections

Spation regulation of V(D)J recombination, schematic (Copyright: IMP)

It is long known that the acquired immune system can generate a vast antibody (immunoglobulin) repertoire by gene recombination in developing B-cells. However, it was not understood how the different immunoglobulin gene segments can meet each other in the three-dimensional space of a B-cell nucleus to undergo recombination, thus generating a functional antibody gene. Scientists from the Vienna BioCenter’s Research Institute of Molecular Pathology (IMP) have now discovered that the transcription factor Pax5 plays a central role in this process by promoting the interaction of immunoglobulin gene segments through cohesin-mediated loop extrusion. These novel findings have been published by Nature today.