title: The human fetal lymphocyte lineage: identification by CD27 and LIN28B expression in B cell progenitors.
abstract: CD27, a member of the TNFR superfamily, is used to identify human memory B cells. Nonetheless, CD27(+) B cells are present in patients with HIGM1 syndrome who are unable to generate GCs or memory B cells. CD27(+)IgD(+) fetal B cells are present in umbilical cord blood, and CD27 may also be a marker of the human B1-like B cells. To define the origin of naïve CD27(+)IgD(+) human B cells, we studied B cell development in both fetal and adult tissues. In human FL, most CD19(+) cells coexpressed CD10, a marker of human developing B cells. Some CD19(+)CD10(+) B cells expressed CD27, and these fetal CD27(+) cells were present in the pro-B, pre-B, and immature/transitional B cell compartments. Lower frequencies of phenotypically identical cells were also identified in adult BM. CD27(+) pro-B, pre-B, and immature/transitional B cells expressed recombination activating gene-1, terminal deoxynucleotidyl transferase and Vpre-B mRNA comparably to their CD27(-) counterparts. CD27(+) and CD27(-) developing B cells showed similar Ig heavy chain gene usage with low levels of mutations, suggesting that CD27(+) developing B cells are distinct from mutated memory B cells. Despite these similarities, CD27(+) developing B cells differed from CD27(-) developing B cells by their increased expression of LIN28B, a transcription factor associated with the fetal lymphoid lineages of mice. Furthermore, CD27(+) pro-B cells efficiently generated IgM(+)IgD(+) immature/transitional B cells in vitro. Our observations suggest that CD27 expression during B cell development identifies a physiologic state or lineage for human B cell development distinct from the memory B cell compartment.
authors.affiliation: 2.DUMC, Durham, NC 27710; ghkelsoe@duke.edu; M.K., E-mail: masayuki.kuraoka@duke.edu.
authors.forename: Laurie
authors.initials: L
authors.lastname: McWilliams
authors.forename: Kuei-Ying
authors.initials: KY
authors.lastname: Su
authors.forename: Xiaoe
authors.initials: X
authors.lastname: Liang
authors.forename: Dongmei
authors.initials: D
authors.lastname: Liao
authors.forename: Serina
authors.initials: S
authors.lastname: Floyd
authors.forename: Joshua
authors.initials: J
authors.lastname: Amos
authors.forename: M Anthony
authors.initials: MA
authors.lastname: Moody
authors.forename: Garnett
authors.initials: G
authors.lastname: Kelsoe
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kuraoka
mesh_terms: D000293:Adolescent; D000328:Adult; D018941:Antigens, CD19 / Q000032:analysis; D019070:Cell Lineage; D004253:DNA Nucleotidylexotransferase / Q000235:genetics; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D005333:Fetus / Q000276:immunology*; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D054444:Immunoglobulin Light Chains, Surrogate / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D008297:Male; D015260:Neprilysin / Q000032:analysis; D017354:Point Mutation; D054448:Precursor Cells, B-Lymphoid / Q000737:chemistry / Q000276:immunology / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D016601:RNA-Binding Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7 / Q000032:analysis*
chemical_list: D018941:Antigens, CD19; D004268:DNA-Binding Proteins; D018398:Homeodomain Proteins; D007143:Immunoglobulin Heavy Chains; D054444:Immunoglobulin Light Chains, Surrogate; D007135:Immunoglobulin Variable Region; C516326:LIN28B protein, human; D012333:RNA, Messenger; D016601:RNA-Binding Proteins; D018127:Tumor Necrosis Factor Receptor Superfamily, Member 7; C515639:VPREB1 protein, human; C064658:RAG-1 protein; D004253:DNA Nucleotidylexotransferase; D015260:Neprilysin
keywords: B cell development; human fetal liver
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