“…While mutations autosomal genes leading to loss of B cell function have been identified in a few rare cases [4], [5,6,7][8,9],, for the great majority of patients, the genetic basis remains unknown. As for other predominantly B cell defects, immunoglobulin (Ig) replacement is the mainstay of treatment, and while this therapy effectively reduces the incidence of bacterial infections, it does not prevent or ameliorate the non-infectious organ-damaging complications which develop in about half of all subjects [10,11]. These complications include hematologic and organ-specific autoimmunity, granulomatous infiltrations, interstitial lung disease, lymphoid hyperplasia, gastrointestinal inflammatory disease, cancer, and lymphoma [12,13,14,15,16].…”