In line with lower anti-OSE IgM titers in human NAFLD (44), an increase in B1-derived natural IgM with specificity for OxLDL resulted in a better outcome for liver disease in atherogenic diet-fed Ldlr−/− mice deficient for the sialic acid-binding immunoglobulin-like lectin G (Siglec-G), a negative regulator of B1 cells and OSE-specific IgM. The gene discussed is CD40LG; the disease is metabolic dysfunction-associated steatotic liver disease.