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Decreased IL7R? and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

ABSTRACT: Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently used proximal V, D and J genes in complete IGH gene rearrangements, despite normal Ig locus contraction. Fewer N-nucleotides were added in IGH gene rearrangements in the context of low TdT and XRCC4 expression. Moreover, fetal progenitor-B cells expressed lower levels of IL7R? than their pediatric counterparts. Analysis of progenitor-B cells from IL7R?-deficient patients revealed that TdT expression and N-nucleotides additions in Dh-Jh junctions were dependent on functional IL7R?. Thus, IL7R? affects TdT expression, and decreased expression of this receptor underlies at least in part the skewed Ig repertoire formation in fetal B-cell precursors. These new insights provide a better understanding of the formation of adaptive immunity in the developing fetus.

SUBMITTER: Rother MB

PROVIDER: S-EPMC5034271 | biostudies-literature | 2016

REPOSITORIES: biostudies-literature

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Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

Rother Magdalena B MB Jensen Kristin K van der Burg Mirjam M van de Bovenkamp Fleur S FS Kroek Roel R van IJcken Wilfred F J WF van der Velden Vincent H J VH Cupedo Tom T Olstad Ole K OK van Dongen Jacques J M JJ van Zelm Menno C MC

Scientific reports 20160923

Newborns are unable to mount antibody responses towards certain antigens. This has been related to the restricted repertoire of immunoglobulin (Ig) genes of their B cells. The mechanisms underlying the restricted fetal Ig gene repertoire are currently unresolved. We here addressed this with detailed molecular and cellular analysis of human precursor-B cells from fetal liver, fetal bone marrow (BM), and pediatric BM. In the absence of selection processes, fetal B-cell progenitors more frequently ...[more]

PMID: 27658954

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Dataset Information

Decreased IL7R? and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

Publications

Decreased IL7Rα and TdT expression underlie the skewed immunoglobulin repertoire of human B-cell precursors from fetal origin.

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