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

Sonja E. Nodland, Magdalena A. Berkowska, Anna A. Bajer, Nisha Shah, Dick De Ridder, Jacques J.M. Van Dongen, Tucker W LeBien, Menno C. Van Zelm

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21 Scopus citations

Abstract

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 VDJH 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 VDJH rearrangements, microarray analysis indicated that CD127+ cells resembled large pre-B cells, which is consistent with their low level of Ig lightchain 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.

Original languageEnglish (US)
Pages (from-to)2116-2127
Number of pages12
JournalBlood
Volume118
Issue number8
DOIs
StatePublished - Aug 25 2011

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    Nodland, S. E., Berkowska, M. A., Bajer, A. A., Shah, N., De Ridder, D., Van Dongen, J. J. M., LeBien, T. W., & Van Zelm, M. C. (2011). IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells. Blood, 118(8), 2116-2127. https://doi.org/10.1182/blood-2010-08-302513