Advisory Committee Chair
John D Mountz
Advisory Committee Members
Date of Award
Degree Name by School
Doctor of Philosophy (PhD) Heersink School of Medicine
Type I IFN is a known pro-inflammatory cytokine that is associated with the development of systemic lupus erythematosus (SLE). At the level of B-cell regulation, current literature primarily attributes the formation of autoantibodies at the post-germinal center stage when type I IFN is known to promote plasmablast differentiation. However, our findings here point to a type I IFN effect at the pre-germinal stage. Type I IFN promotes T-dependent antibody response, activation-induced cytidine deaminase (AID) expression, germinal center formation, all of which are processes before the onset of plasmablast differentiation. We have determined a subset of splenic transitional B-cells, that is known as the precursors to the development of marginal zone (MZ) B-cell population, and are termed marginal zone B-cell precursors (MZPs), whose trafficking from the MZ border to the inner follicle (FO) is promoted by type I IFN. MZPs are more efficient antigen-presenting cells than MZ or FO B cells. Type I IFN up-regulates expression of CD69 and down-regulates expression of S1P1 to promote migration of MZPs into the inner follicle to interact with CD4 T-cells. Together, these observations suggest a novel pathway by which type I IFN can promote the presentation of antigen to CD4 T-cells by MZPs to initiate germinal center reaction prior to type I IFN induction of plasmablast differentiation.
Wang, John Hsien, "Marginal zone B-cell precursors as cellular agents for type I IFN promoted antigen transport" (2009). All ETDs from UAB. 3251.