title: Cutting Edge: defective follicular exclusion of apoptotic antigens due to marginal zone macrophage defects in autoimmune BXD2 mice.
abstract: 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.
authors.affiliation: Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35294, USA.
authors.forename: Hao
authors.initials: H
authors.lastname: Li
authors.forename: Qi
authors.initials: Q
authors.lastname: Wu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: PingAr
authors.initials: P
authors.lastname: Yang
authors.forename: Zilu
authors.initials: Z
authors.lastname: Zhu
authors.forename: Bao
authors.initials: B
authors.lastname: Luo
authors.forename: Hui-Chen
authors.initials: HC
authors.lastname: Hsu
authors.forename: John D
authors.initials: JD
authors.lastname: Mountz
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000276:immunology*; D001324:Autoantigens / Q000276:immunology*; D015551:Autoimmunity / Q000276:immunology; D001402:B-Lymphocytes / Q000276:immunology; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D002465:Cell Movement / Q000276:immunology; D007108:Immune Tolerance / Q000276:immunology; D008264:Macrophages / Q000276:immunology*; D051379:Mice; D008810:Mice, Inbred C57BL
chemical_list: D001324:Autoantigens
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