The mechanisms whereby B-1a B cell-derived IgM can protect from atherosclerosis have been best characterized using the prototypic monoclonal IgM antibody, E06 (Chang et al., 1999, 2004; Hörkkö et al., 1999; Shaw et al., 2000; Binder et al., 2003; Chou et al., 2009). The gene discussed is CD40LG; the disease is atherosclerosis.