title: IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells.
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 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.
authors.affiliation: Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA.
authors.forename: Sonja E
authors.initials: SE
authors.lastname: Nodland
authors.forename: Magdalena A
authors.initials: MA
authors.lastname: Berkowska
authors.forename: Anna A
authors.initials: AA
authors.lastname: Bajer
authors.forename: Nisha
authors.initials: N
authors.lastname: Shah
authors.forename: Dick
authors.initials: D
authors.lastname: de Ridder
authors.forename: Jacques J M
authors.initials: JJ
authors.lastname: van Dongen
authors.forename: Tucker W
authors.initials: TW
authors.lastname: LeBien
authors.forename: Menno C
authors.initials: MC
authors.lastname: van Zelm
mesh_terms: D000818:Animals; D018941:Antigens, CD19 / Q000378:metabolism; D002454:Cell Differentiation / Q000276:immunology; D019070:Cell Lineage / Q000276:immunology; D018920:Coculture Techniques; D004253:DNA Nucleotidylexotransferase / Q000378:metabolism; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D020869:Gene Expression Profiling; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D006801:Humans; D015851:Interleukin-7 / Q000378:metabolism*; D053699:Interleukin-7 Receptor alpha Subunit / Q000378:metabolism*; D051379:Mice; D010641:Phenotype; D054448:Precursor Cells, B-Lymphoid / Q000166:cytology* / Q000276:immunology*; D015398:Signal Transduction
chemical_list: D018941:Antigens, CD19; C508605:IL7 protein, human; D015851:Interleukin-7; D053699:Interleukin-7 Receptor alpha Subunit; D004253:DNA Nucleotidylexotransferase