TY - JOUR
T1 - IL-7R expression and IL-7 signaling confer a distinct phenotype on developing human B-lineage cells
AU - Nodland, Sonja E.
AU - Berkowska, Magdalena A.
AU - Bajer, Anna A.
AU - Shah, Nisha
AU - De Ridder, Dick
AU - Van Dongen, Jacques J.M.
AU - LeBien, Tucker W
AU - Van Zelm, Menno C.
PY - 2011/8/25
Y1 - 2011/8/25
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=80052153064&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=80052153064&partnerID=8YFLogxK
U2 - 10.1182/blood-2010-08-302513
DO - 10.1182/blood-2010-08-302513
M3 - Article
C2 - 21680796
AN - SCOPUS:80052153064
SN - 0006-4971
VL - 118
SP - 2116
EP - 2127
JO - Blood
JF - Blood
IS - 8
ER -