Abnormalities in DNA double-strand break response beyond primary immunodeficiency

V(D)J recombination and class switch recombination are achieved by the cooperative processes of recombination activation gene- or activation-induced cytidine deaminase-dependent DNA cleaving, DNA double-strand break (DSB) response signaling, and DNA repair. Primary immunodeficiency due to dysfunctional DNA recombination can be categorized as severe combined immunodeficiency or other conditions, based on the presence or absence of T cells. We can also classify these diseases as radiosensitive or non-radiosensitive immunodeficiencies. While diseases unable to trigger DNA cleavage do not exhibit radiosensitivity, dysfunction in DSB response signaling or repair does lead to radiosensitive immunodeficiency. Recent studies have begun to clarify the mechanisms underlying the molecular pathogenesis of such DNA DSB-related primary immunodeficiency.