title: Striking decrease in the total precursor B-cell compartment during early childhood as evidenced by flow cytometry and gene expression changes.
abstract: The number of circulating B-cells in peripheral blood plateaus between 2 and 24 months of age, and thereafter declines gradually. How this reflects the kinetics of the precursor B-cell pool in the bone marrow is of clinical interest, but has not been studied thoroughly in humans. The authors analyzed bone marrow (n = 37) from healthy children and adults (flow cytometry) searching for age-related changes in the total precursor B-cell compartment. In an age-matched cohort (n = 25) they examined age-related global gene expression changes (Affymetrix) in unsorted bone marrow with special reference to the recombination activating gene 1, RAG1. Subsequently, they searched the entire gene set for transcripts correlating to the RAG1 profile to discover other known and possibly new precursor B-cell related transcripts. Both methods disclosed a marked, transient increase of total precursor B-cells at 6-20 months, followed by a rapid decrease confined to the first 2 years. The decline thereafter was considerably slower, but continued until adulthood. The relative composition of total precursor B-cells, however, did not change significantly with age. The authors identified 54 genes that were highly correlated to the RAG1 profile (r >or= .9, p < 1 x 10(-8)). Of these 54 genes, 15 were characteristically B-lineage associated like CD19, CD79, VPREB, EBF1, and PAX5; the remaining 39 previously not described as distinctively B-lineage related. The marked, transient increase in precursor B-cells and RAG1 transcriptional activity is not reflected by a similar peak in B-cells in peripheral blood, whereas the sustained plateau concurs in time.
authors.affiliation: Department of Pediatrics, Faculty Division Ullevål, University of Oslo, Oslo, Norway. kristin.jensen@medisin.uio.no
authors.forename: Kristin
authors.initials: K
authors.lastname: Jensen
authors.forename: Lana
authors.initials: L
authors.lastname: Schaffer
authors.forename: Ole K
authors.initials: OK
authors.lastname: Olstad
authors.forename: Anne G
authors.initials: AG
authors.lastname: Bechensteen
authors.forename: Marit
authors.initials: M
authors.lastname: Hellebostad
authors.forename: Geir E
authors.initials: GE
authors.lastname: Tjønnfjord
authors.forename: Peter
authors.initials: P
authors.lastname: Kierulf
authors.forename: Kaare M
authors.initials: KM
authors.lastname: Gautvik
authors.forename: Liv T N
authors.initials: LT
authors.lastname: Osnes
mesh_terms: D000293:Adolescent; D000328:Adult; D000375:Aging / Q000097:blood* / Q000276:immunology; D016175:B-Lymphocyte Subsets; D001853:Bone Marrow / Q000254:growth & development; D001856:Bone Marrow Examination; D019070:Cell Lineage; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D005434:Flow Cytometry; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006412:Hematopoietic Stem Cells; D018398:Homeodomain Proteins / Q000096:biosynthesis / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018655:Lymphocyte Count; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D014158:Transcription, Genetic; D055815:Young Adult
chemical_list: D018398:Homeodomain Proteins; D012333:RNA, Messenger; C064658:RAG-1 protein