Daniela Gomez Atria

"Stromal Notch ligands drive Notch2-dependent transdifferentiation of follicular B cells into marginal zone-like B cells in lymphopenic environments"

Lymphopenic environments, like those induced during irradiation or viral infections, allow the homeostatic proliferation of newly transferred lymphocytes. The molecular mechanisms underlying this process and its functional consequences are largely unknown. Here we demonstrate that highly purified mouse follicular B cells (FoB) can transdifferentiate into marginal zone (MZ)-like B cells when transferred into lymphopenic hosts. During this process the transferred B cells lose their FoB phenotype and gradually acquire characteristic of MZ B cells, as judged by their surface phenotype, anatomical localization, and function. This process preceeds proliferation and the degree of this response is dictated by the extent of B cell lymphopenia in the host. Furthermore, the transdifferentiation process is largely dependent on Notch2 and the expression of the delta-like ligand 1 (Dll1) by spleen stromal cells. Thus, resembling the traditional developmental requirements of MZ B cells. Therefore, we postulate that stromal DLL1 Notch ligands are critical to regulate the size and composition of the splenic peripheral B cell pool in lymphopenic mice through interactions with Notch2. Furthermore, FoB cells are not locked in their FoB cell fate, as commonly assumed, but are instead endowed with plastic transdifferentiation potential in response to DLL1/Notch2-mediated signals during lymphopenia.