Mr. Hao Li received his M.S. degree from the Institute of Medicinal Biotechnology of the Chinese Academy of Medical Science in 2005. He joined the Hao LiGraduate Program in Microbiology at UAB in 2008 and has carried out his graduate study in Dr. John Mountz laboratory at UAB since 2008.  Mr. Li initially studied the role of IL-23 in the regulation of autoimmune disease in the BXD2 mouse model of systemic autoimmunity.  These mice develop spontaneous germinal centers (GCs) in the spleen that are highly dependent of interleukin (IL)-17.  Mr. Li made the novel and unexpected finding that IL-23 was necessary to maintain the integrity of marginal zone barrier that prevents follicular entry of apoptotic self-antigens in BXD2 mice.  This initial work led to his present findings of a novel mechanism of autoimmunity in which “leaks” in the marginal zone barrier enable entry of apoptotic Ags into the follicle Mr. Li currently studies the molecular mechanisms regulating the interactions of marginal zone macrophages and marginal zone B cells in maintaining the tolerogenic function of these cells to apoptotic self-antigens.

 Research interests of Mountz's lab.

Dr. John D. Mountz's primary research interest has been to understand how dysregulation of apoptosis affects the development of autoimmune diseases.  Dr. Mountz was one of the first investigators to propose that autoimmunity is caused by a defect in apoptosis.  In the course of the present studies, Dr. Mountz discovered that the BXD2 strain of mice exhibits early-age onset of massive splenomegaly, produces highly-pathogenic autoantibodies, and spontaneously develops large, fully-developed GCs.  Detailed characterization of these mice led to the first observation that the production of IL-17 by Th17 cells in the spontaneous GCs was necessary for development of autoreactive B cells.  Dr. Mountz then demonstrated that the IL-17 acts to regulate the migration of the cells that form the GCs. It induces upregulation of Regulator of G-protein signaling (RGS)13 and RGS16, which is signaled directly in B cells through the canonical NF-κB pathway and results in migration arrest of GC B cells in response to CXCL13, thereby prolonging their interaction with follicular T helper cells in the light zone of GCs.  A remaining question was what triggers activation of autoreactive T and B cells in BXD2 mice.  Mr. Li’s new finding is a logical extension of Dr. Mountz past interests in apoptosis, macrophages, development of spontaneous GCs, and gene therapy to correct autoimmune defects.  Dr. Mountz and colleagues are currently developing a liposome drug/gene delivery approach to correct regulatory defects in marginal zone macrophages that are responsible for clearance of apoptotic bodies in the spleen of autoimmune mice.

J Immunol. 2013 Mar 29. [Epub ahead of print]

Cutting Edge: Defective Follicular Exclusion of Apoptotic Antigens Due to Marginal Zone Macrophage Defects in Autoimmune BXD2 Mice.

Li H, Wu Q, Li J, Yang P, Zhu Z, LuoHYPERLINK ";cauthor=true&cauthor_uid=23543760" B, Hsu HC, Mountz JD.

Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294;


Marginal zone macrophages (MZMs) act as a barrier to entry of circulating apoptotic debris into the follicles of secondary lymphoid organs. In autoimmune BXD2 mice, there is a progressive reduction in the function and numbers of MZMs. Absence of MZMs results in retention of apoptotic cell (AC) debris within the marginal zone (MZ) and increased loading of AC Ags on MZ B cells and MZ-precursor (MZ-P) B cells. The MZ-P B cells are capable of translocating the AC Ags to the follicular zone and stimulating T cells. Both MZMs and MZ-P B cells from BXD2 mice express low levels of tolerogenic signals and high levels of inflammatory signals. Thus, the current study suggests a multifaceted mechanism in which MZMs maintain tolerance to apoptotic autoantigens and suppress their translocation to follicles. Lack of clearance of apoptotic debris by MZMs drives follicular Ag-transportation by MZ-P B cells to stimulate an autoimmune response.

  Click here for PDF