ZBTB20 is an adjuvant-specific regulator of long-term antibody responses (P1439)

Abstract

Abstract The duration of antibody production following immunization can vary greatly depending on the vaccine, but the molecular basis for these differences is unknown. Here, we demonstrated that ZBTB20 is an adjuvant-specific transcription factor critical for the durable antibody production by long-lived plasma cells. ZBTB20 was highly expressed in germinal center and memory B cells and in short and long-lived plasma cells, but not in naïve B cells.Zbtb20 deficiency due to a gene trap mutation in the Zbtb20 locus specifically led to defective accumulation of long-lived plasma cells following immunization, while short-lived plasmablasts and germinal center B cells were unaffected. Competitive fetal liver reconstitution experiments demonstrated a B cell-intrinsic requirement for ZBTB20 in long-term antibody production following alum-adjuvanted immunization. Strikingly, inclusion of Toll-like receptor ligands in the adjuvant completely rescued long-term antibody production in Zbtb20-deficient fetal liver chimeras. Thus, different immunization conditions induce long-lived plasma cells with qualitatively distinct transcriptional programs to regulate their turn-over.