IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells

IL-7 is an important cytokine for lymphocyte differentiation. Similar to what occurs in vivo, human CD19⁺ cells developing in human/murine xenogeneic cultures show differential expression of the IL-7 receptor α (IL-7Rα) chain (CD127). We now describe the relationship between CD127 expression/signaling and Ig gene rearrangement. In the present study, < 10% of CD19⁺CD127⁺ and CD19⁺CD127⁻ populations had complete VDJ(H) rearrangements. IGH locus conformation measurements by 3D FISH revealed that CD127⁺ and CD127⁻ cells were less contracted than pediatric BM pro-B cells that actively rearrange the IGH locus. Complete IGH rearrangements in CD127⁺ and CD127⁻ cells had smaller CDR3 lengths and fewer N-nucleotide insertions than pediatric BM B-lineage cells. Despite the paucity of VDJ(H) rearrangements, microarray analysis indicated that CD127⁺ cells resembled large pre-B cells, which is consistent with their low level of Ig light-chain rearrangements. Unexpectedly, CD127⁻ cells showed extensive Ig light-chain rearrangements in the absence of IGH rearrangements and resembled small pre-B cells. Neutralization of IL-7 in xenogeneic cultures led to an increase in Ig light-chain rearrangements in CD127⁺ cells, but no change in complete IGH rearrangements. We conclude that IL-7-mediated suppression of premature Ig light-chain rearrangement is the most definitive function yet described for IL-7 in human B-cell development.