Mer (MerTK), a member of the Tyro-3/Axl/Mer subfamily receptor tyrosine kinases, expression on phagocytes facilitates their clearance of apoptotic cells (ACs). Mer expression in germinal centers (GCs) occurs predominantly on tingible body macrophages. B and T cells do not express Mer. Mer deficiency (Mer-/-) results in the accumulation of ACs in GCs and augmented antibody-forming cell (AFC), GC and IgG2 Ab responses against T-dependent (TD) Ag. Here, we show that AC accumulation in GCs and elevated AFC, GC and IgG2 Ab responses in Mer-/- mice lasted for at least 80 days after immunization with NP-OVA. Enhanced responses and AC accumulation in Mer -/- GCs were associated with increased activation and proliferation of B cells and activated effector helper T cells, including follicular T (Tfh) cells. Secondary IgG-producing AFC, total IgG and IgG2 Ab responses were also increased in Mer -/- mice. Augmented B and T cell responses and long-term AC accumulation in Mer -/- mice compared to wild type (WT) controls. Together, these results highlight the important role of AC clearance by Mer in regulating GC B cell, helper T cell and autoantibody responses and in maintaining peripheral B cell tolerance.
Recommended CitationKhan, Tahsin N.; Wong, Eric B.; and Rahman, Ziaur S.M., "Effects of apoptotic cell accumulation caused by Mer deficiency on germinal center B cells and helper T cells" (2012). Department of Microbiology and Immunology Faculty Papers. Paper 28.