title: Novel diversity in IL-4-mediated responses in resting human naive B cells versus germinal center/memory B cells.
abstract: Recent studies have defined several phenotypic and molecular changes associated with the maturation of naive human B cells within the milieu of germinal centers. Although naive B cells serve as natural precursors to germinal center (GC)/memory (M) subpopulations, little is known about the physiological requirements for the survival of the naive B cell pool in the absence of cell-cell contact or Ag-mediated activation. Because IL-4 induces expression of several membrane receptors such as CD23 which are uniquely present on resting human naive B lymphocytes, we hypothesized that these cells might be intrinsically programmed to respond to IL-4 in the absence of cell division. Using buoyant density-dependent isolation and further enrichment by negative/positive selection of human naive and GC/M subpopulations, we characterized cytokine receptor moieties on these cells and analyzed their survival and growth in the presence of IL-4 or IL-10. Resting naive B cells expressed significantly higher IL-4 receptor alpha-chain on their cell surface than the combined GC/M subpopulation. The IL-10 receptor and the IL-2 receptor gammac chain were almost equally expressed on both subpopulations. When cultured in vitro, the addition of IL-4, but not IL-10, protected naive B cells from apoptosis in the absence of activation and growth. However, IL-4 exerted no such effect on resting GC/M B cells. These data support the hypothesis that IL-4 plays a pivotal role in the survival and maintenance of resting human naive B cells.
authors.affiliation: Departments of Pediatrics and Pathology, Women & Infants' Hospital and Department of Medicine, Rhode Island Hospital, Brown University, Providence, RI 02905, USA.
authors.forename: E F
authors.initials: EF
authors.lastname: Wagner
authors.forename: N
authors.initials: N
authors.lastname: Hanna
authors.forename: L D
authors.initials: LD
authors.lastname: Fast
authors.forename: N
authors.initials: N
authors.lastname: Kouttab
authors.forename: P R
authors.initials: PR
authors.lastname: Shank
authors.forename: A
authors.initials: A
authors.lastname: Vazquez
authors.forename: S
authors.initials: S
authors.lastname: Sharma
mesh_terms: D000276:Adjuvants, Immunologic / Q000502:physiology; D000954:Antigens, Surface / Q000032:analysis; D016175:B-Lymphocyte Subsets / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D015415:Biomarkers / Q000032:analysis; D016923:Cell Death / Q000276:immunology; D002455:Cell Division / Q000276:immunology; D048429:Cell Size / Q000276:immunology; D002470:Cell Survival / Q000276:immunology; D002478:Cells, Cultured; D018858:Germinal Center / Q000737:chemistry / Q000166:cytology* / Q000276:immunology*; D006801:Humans; D007156:Immunologic Memory; D016130:Immunophenotyping; D015847:Interleukin-4 / Q000502:physiology*; D007399:Interphase / Q000276:immunology; D008213:Lymphocyte Activation / Q000276:immunology; D018655:Lymphocyte Count; D014066:Palatine Tonsil / Q000166:cytology; D019948:Receptors, Interleukin-4 / Q000096:biosynthesis
chemical_list: D000276:Adjuvants, Immunologic; D000954:Antigens, Surface; D015415:Biomarkers; D019948:Receptors, Interleukin-4; D015847:Interleukin-4