Germinal center-independent, IgM-mediated autoimmunity in sanroque mice lacking Obf1
Stephane Chevrier, Tobias Kratina, Dianne Emslie, Alexander Karnowski, Lynn M Corcoran
Immunology and Cell Biology | NATURE PUBLISHING GROUP | Published : 2014
Mice homozygous for a point mutation in the Rc3h1 gene encoding Roquin1, designated sanroque mice, develop a severe antibody-mediated autoimmune condition. The disease is T-cell intrinsic, exacerbated by macrophage-intrinsic defects and driven by excessive T follicular helper cell generation and spontaneous germinal centre (GC) formation. This culminates in abnormally high numbers of plasma cells secreting high-affinity autoreactive immunoglobulin G (IgG). Obf1 is a transcriptional co-activator required for normal T-cell-dependent antibody responses, and it is essential for GC formation under all circumstances so far tested. We crossed sanroque mice with Obf1-null mice to determine whether t..View full abstract
Awarded by NHMRC
We are indebted to Professor Carola Vinuesa for Sanroque mice and for many helpful comments during this work and on the manuscript. We are also extremely grateful to Professor Donald Metcalf for histology and pathology, to Dr Lachlan Whitehead for help with immunofluorescence, to Kathy D'Costa for technical assistance and to Louise Inglis for animal husbandry. This work was made possible through the Victorian State Government Operational Infrastructure Support and the Australian Government NHMRC IRIIS and research grants from the NHMRC (No. 637306 and No. 575500).