Follicular dendritic cells control engulfment of apoptotic bodies by secreting Mfge8

Abstract

The secreted phosphatidylserine-binding protein milk fat globule epidermal growth factor 8 (Mfge8) mediates engulfment of apoptotic germinal center B cells by tingible-body macrophages (TBMφs). Impairment of this process can contribute to autoimmunity. We show that Mfge8 is identical to the mouse follicular dendritic cell (FDC) marker FDC-M1. In bone-marrow chimeras between wild-type and Mfge8−/− mice, all splenic Mfge8 was derived from FDCs rather than TBMφs. However, Mfge8−/− TBMφs acquired and displayed Mfge8 only when embedded in Mfge8+/+ stroma, or when situated in lymph nodes draining exogenous recombinant Mfge8. These findings indicate a licensing role for FDCs in TBMφ-mediated removal of excess B cells. Lymphotoxin-deficient mice lacked FDCs and splenic Mfge8, and suffer from autoimmunity similar to Mfge8−/− mice. Hence, FDCs facilitate TBMφ-mediated corpse removal, and their malfunction may be involved in autoimmunity.