Although somatic hypermutation can contribute to both gain and loss of self-reactivity and autoimmunity may be caused by both follicular and extrafollicular pathways, molecular defects (i.e., DNASE1L3 and IKZF1 deficiency) have been shown to drive extrafollicular SLE (Al-Mayouf et al., 2011; Jenks et al., 2019; Schwickert et al., 2019; Soni et al., 2020; Van Nieuwenhove et al., 2018). Here, DNASE1L3 is linked to Autoimmunity.