Lymph node lymphangiogenesis constrains the germinal center structure to enhance selection and functional antibody production during cutaneous virus infection
Presentation Time: 09:45 AM - 10:00 AM
Abstract ID: 4436 - B
Presenting Author:
Luan Firmino Cruz , Post-Doc at NYU Grossman Sch. of Med.
Abstract:
Germinal centers (GCs) form in B cell follicles after immunization or infections. Naive B cells enter GCs to increase affinity through somatic hypermutation to then become antibody producing long-lived plasma cells. Stromal cells provide an important scaffold of lymphocyte organization in lymph nodes (LN) and can directly regulate GC structure through the production of supportive chemokines/cytokines. During cutaneous viral infection we observed vascular endothelial growth factor receptor 2 (VEGFR2)-dependent lymphangiogenesis, which led to lymphatic sprouting around B cell follicles during GC reaction, however the impact of lymphatic growth on the functional germinal center response is yet to be investigated.To investigate the impact of perifollicular lymphangiogenesis in the GC response, we used a localized infection by vaccinia virus (VacV, scarification) to induce GCs in draining LNs of mice lacking expression of VEGFR2 in lymphatic vessels. With VEGFR2-deficient lymphatic vessels, draining LNs show decreased perifollicular lymphatic growth and a surprising increase in GC area, which associated with lower levels of VacV-specific IgG2b. To determine whether the change in GC structure altered functionality, we blocked VEGFR2 in GC B cells fate-mapper Aicdacre/+ Rosa26Confetti/Confetti mice, here GCs exhibited less selection, which together with reduced VacV-specific IgG2b indicates that lymphatic-dependent GC restraint optimizes GC fitness and thereby anti-viral immunity.
Lymph node lymphangiogenesis constrains the germinal center structure to enhance selection and functional antibody production during cutaneous virus infection
Category
Poster and Podium (Block Symposium)