IL-7Rα deficiency impairs the differentiation and expansion of early BCPs. (A) Overview of the IL-7Rα chain with the individual domains and motifs highlighted as shown in the figure. Top graph shows the gene with exons marked as boxes; bottom graph shows the protein. Extracellular domain (blue) with fibronectin type 3–like domains DN1 and DN2 and 4 paired cysteine residues indicated by blue circles as well as WS × WS motif; transmembrane domain (orange); intracellular domain (yellow) with four-point-one protein, ezrin, radixin, moesin (FERM) domain, BOX1 domain, and 3 tyrosine residues indicated by red circles. The mutations of the 2 patients are indicated by arrows. One patient had a homozygous premature nonsense mutation (red), whereas the other patient had a heterozygous splice acceptor site mutation (blue) and a chromosomal deletion of the other allele. (B) Markers used for the definition of the human BCP populations with the corresponding stages of V(D)J recombination. Markers that are strongly expressed by the given population are depicted in bold, whereas a lack of expression is shown in gray. (C) Flow cytometric analysis of the BCP stages in the BM, shown for 1 representative pediatric control and 1 patient. (D) Relative cell counts of the BCP stages in pediatric controls (n = 10) and the 2 patients with IL-7Rα deficiency. Data show median with range. (E) Distribution of BCP stages in pediatric controls (n = 10) and the 2 patients with IL-7Rα deficiency. Data show the median of each population. (F) Expression of the IL-7Rα chain (CD127) on the individual human BCP subsets in the BM of a healthy pediatric control compared with a patient with IL-7Rα deficiency. UTR, untranslated region.