The Role of DOT1L in B-Cell Biology

This thesis examined the role of the histone lysine 79 methyltransferase, DOT1L, in the regulation of B-cell biology. We showed that DOT1L is playing a key role in the early development of B-lymphocytes and in the V(D)J recombination events that establish a diverse B-cell receptor repertoire. In addition to this, we revealed a critical role for DOT1L in the formation and regulation of the germinal centre reaction via H3K79 methylation of key target genes. In this way, DOT1L plays a vital role in establishing effective and lasting humoral immunity to vaccination and infection and in regulating different stages of B-cell biology.