Reduced B cell activation in Germinal center reaction of the mouse model of Li-Fraumeni syndrome

Abstract The TP53 mutation associated with Li-Fraumeni syndrome in humans is known to exhibit p53 gain-of-function properties leading to early cancer onset. To explore whether these patients also have compromised immune responses due to p53 mutations, we investigated the humoral immune response using a Li-Fraumeni mouse model harboring a structural mutation, Trp53R172H (equivalent to codon 175 in humans). Trp53R172H mice were immunized with sheep red blood cells, and the Germinal center response was monitored. Our results revealed that SRBC-immunized Trp53R172H mice exhibit reduced B cell activation during the GC reaction. These suggest a selective role for p53 in promoting B cell activation early in the GC reaction prior to BCL6 upregulation. We propose that impaired B cell activation in Li-Fraumeni patients could contribute to immune deficiencies and heightened susceptibility to autoimmune disorders, potentially influencing the development of secondary cancers and impairing therapeutic responses to chemotherapies and immunotherapies. Key Points Trp52R172H mice exhibit reduced B cell activation during the Germinal center reaction Ratio of activated B cells in DZ to LZ remain unchanged in Trp52R172H mice.