Advisory Committee Chair
John D Mountz
Advisory Committee Members
David D Chaplin
Chander Raman
Etty Benveniste
Hubert M Tse
Janusz H Kabarowski
Document Type
Dissertation
Date of Award
2014
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Abstract
Systemic lupus erythematosus (SLE) is characterized by elevation of type I interferon (IFN) signature genes and production of autoantibodies against apoptotic self-antigens. The complex nature of SLE, however, suggests that multiple immune dysregulations must integrate to initiate the disease. Here, we provided evidence that lupus can be initiated via type I IFNs-induced follicular translocation of membrane lymphotoxin (mLT)-expressing marginal zone (MZ) B cells in the spleen of lupus prone BXD2 mice. The mislocation of mLT+ MZ B cells induces two important pathogenic effects including deteriorations of marginal zone macrophages (MZMs) in the MZ, leading to defective clearance of apoptotic debris, and activation of follicular dendritic cells (FDCs), leading to the formation of germinal centers (GCs). These abnormal features are abrogated in BXD2-Ifnαr-/- mice. Thus, apoptotic antigens, loss of MZMs and activation of FDCs are ultimately connected via type I IFNs-induced invasion of innate B cells to initiate lupus.
Recommended Citation
Li, Hao, "Type I Interferons-induced Follicular Translocation of Lymphotoxin-Expressing Marginal Zone B cells Initiates Lupus" (2014). All ETDs from UAB. 2271.
https://digitalcommons.library.uab.edu/etd-collection/2271