Germinal centers (GCs) are specialized micro-environments that generate high affinity Ab-forming cells (AFCs) and memory B cells. Many B cells undergo apoptosis during clonal selection in GCs. The TAM (Tyro-3, Axl, and Mer) family receptor tyrosine kinases, including Mer, facilitate macrophage clearance of apoptotic cells. We previously showed that tingible body macrophages (TBMφs) in GCs express Mer. We observed that apoptotic cells (ACs) accumulated in GCs of mice deficient in Mer (Mer-/-), after immunization with T-dependent Ag. Accumulation of ACs in GCs of Mer-/- mice resulted in significantly increased AFCs, GCs, and Th1-skewed IgG2c Ab responses. We report here that increased GC response in Mer-/- mice compared to controls is due to increased proliferation of GC B cells. We also found that AC accumulation in Mer-/- GCs is not due to increased B cell apoptosis. We show that TBMφs express two other members (Tyro-3 and Axl) of TAM family receptors, which are similar in both Mer-/- and controls. TBMφs in GCs of both strains express similar levels of milk fat globule EGF factor 8 (Mfge8) and T cell immunoglobulin 4 (Tim-4), which are believed to aid in AC clearance. These data indicate the critical role for Mer in the clearance of ACs in GCs. This is further strengthened by the efficient clearance of ACs from GCs in mice deficient in Axl (Axl-/-) in the presence of Mer. Together, these data demonstrate a pivotal role of Mer in regulating B cell response and in the maintenance of B cell tolerance.
Recommended CitationKhan, Tahsin N.; Wong, Eric B.; and Rahman, PhD, Ziaur S.M., "The Role of Mer in Apoptotic Cell Clearance in the Germinal Center" (2011). Department of Microbiology and Immunology Faculty Papers. Paper 15.