Expression profiles of murine FOXO1+/+ and FOXO1-null GC B cells

The pathways regulating the formation of the germinal center (GC) dark- (DZ) and light- (LZ) zones are unknown. We show that FOXO1 expression is restricted to the GC DZ and is required for DZ formation, since its absence in mice leads to the complete loss of DZ gene programs and the formation of LZ-only GCs. FOXO1-negative GC B-cells display normal somatic hypermutation, but defective affinity maturation and class switch recombination. The function of FOXO1 in sustaining the DZ program involves the transactivation of the chemokine receptor CXCR4, and the cooperation with BCL6 in the trans-repression of genes involved in immune activation, DNA-repair and plasma cell differentiation. These results have also implications for understanding the role of FOXO1 mutations in lymphomagenesis.

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Dominguez-Sola D, Kung J, Holmes AB, Wells VA, Mo T, Basso K, Dalla-Favera R