title: Expansion of functionally immature transitional B cells is associated with human-immunodeficient states characterized by impaired humoral immunity.
abstract: X-linked lymphoproliferative disease (XLP) is a severe immunodeficiency associated with a marked reduction in circulating memory B cells. Our investigation of the B cell compartment of XLP patients revealed an increase in the frequency of a population of B cells distinct from those previously defined. This population displayed increased expression of CD10, CD24, and CD38, indicating that it could consist of circulating immature/transitional B cells. Supporting this possibility, CD10+CD24highCD38high B cells displayed other immature characteristics, including unmutated Ig V genes and elevated levels of surface IgM; they also lacked expression of Bcl-2 and a panel of activation molecules. The capacity of CD24highCD38high B cells to proliferate, secrete Ig, and migrate in vitro was greatly reduced compared with mature B cell populations. Moreover, CD24highCD38high B cells were increased in the peripheral blood of neonates, patients with common variable immunodeficiency, and patients recovering from hemopoietic stem cell transplant. Thus, an expansion of functionally immature B cells may contribute to the humoral immunodeficient state that is characteristic of neonates, as well as patients with XLP or common variable immunodeficiency, and those recovering from a stem cell transplant. Further investigation of transitional B cells will improve our understanding of human B cell development and how alterations to this process may precipitate immunodeficiency or autoimmunity.
authors.affiliation: Centenary Institute of Cancer Medicine and Cell Biology, New South Wales, Australia.
authors.forename: Amanda K
authors.initials: AK
authors.lastname: Cuss
authors.forename: Danielle T
authors.initials: DT
authors.lastname: Avery
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Cannons
authors.forename: Li Jun
authors.initials: LJ
authors.lastname: Yu
authors.forename: Kim E
authors.initials: KE
authors.lastname: Nichols
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Shaw
authors.forename: Stuart G
authors.initials: SG
authors.lastname: Tangye
mesh_terms: D051997:ADP-ribosyl Cyclase 1 / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000361:Agammaglobulinemia / Q000276:immunology* / Q000473:pathology*; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism / Q000473:pathology*; D051927:CD24 Antigen / Q000096:biosynthesis; D018956:CD5 Antigens / Q000276:immunology; D002454:Cell Differentiation / Q000276:immunology*; D002455:Cell Division / Q000276:immunology*; D002465:Cell Movement / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D002648:Child; D005312:Fetal Blood / Q000166:cytology / Q000276:immunology; D006801:Humans; D007135:Immunoglobulin Variable Region / Q000096:biosynthesis / Q000235:genetics; D008232:Lymphoproliferative Disorders / Q000276:immunology* / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis; D008875:Middle Aged
chemical_list: D051927:CD24 Antigen; D018956:CD5 Antigens; D007135:Immunoglobulin Variable Region; D008562:Membrane Glycoproteins; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1