Major Achievements

The activity of specific sets of members of the NF-kB family of transcription factors is controlled by two distinct activation pathways, the canonical and the alternative NF-kB signaling pathways. We demonstrated that NF-kB signaling was critically required at specific stages of B cell development.

In the bone marrow, these signals are essential during early B cell development for the generation of B cells expressing a B cell antigen receptor (BCR) comprising Igl, one of the two Immunoglobulin light chains possible.

In the periphery, resting mature follicular B cells have been shown to rely on the PI3K – Foxo1 axis downstream of the BCR for their persistence, the so-called tonic survival signals. We established that these cells also require signaling from the canonical NF-kB pathway for their maintenance. However, these signals are specifically needed for the long-term persistence of mature follicular B cells.

The contribution of NF-kB signaling to the generation of Igl+ B cells and the maintenance of mature B cells appears to depend on its ability to positively modulate cell survival.