NGFR regulates germinal center B-cell activation and negative selection

Abstract

AbstractThe expression of the Nerve growth factor receptor (NGFR) has been described in follicular dendritic cells (FDCs), the major lymphoid stromal cell (LSC) compartment regulating B-cell activation within germinal centers (GCs). However, the role of NGFR in humoral response is not well defined. In this work, we have studied the effect ofNgfrKO in LNs organization and function.NgfrKO led to spontaneous GC formation and expansion of GC B-cell compartment which were related toNgfrdepletion in non-hematopoietic radioresistant compartment. In agreement,NgfrKO mice showed alterations in LSC with an increased frequency of FDCs harboring an activated phenotype characterized by the overexpression of CD21/35, MAdCAM-1, and VCAM-1. Moreover,NgfrKO mice showed GC ectopic location, loss of polarization, impaired high-affinity antibody production, and increased circulating autoantibodies. In addition,NgfrKO/Bcl2Tg mice displayed increased levels of autoantibodies, higher incidence of autoimmunity, and decreased overall survival. Our work shows that NGFR maintains GC structure and functionality, being involved in the regulation of antibody production and immune tolerance.