title: B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients.
abstract: Around 65% of primary immunodeficiencies are antibody deficiencies. Functional tests are useful tools to study B-cell functions in vitro. However, no accepted guidelines for performing and evaluating functional tests have been issued yet. Here, we report our experience on the study of B-cell functions in infancy and throughout childhood. We show that T-independent stimulation with CpG measures proliferation and differentiation potential of memory B cells. Switched memory B cells respond better than IgM memory B cells. On the other hand, CD40L, a T-dependent stimulus, does not induce plasma cell differentiation, but causes proliferation of naïve and memory B cells. During childhood, the production of plasmablasts in response to CpG increases with age mirroring the development of memory B cells. The response to CD40L does not change with age. In patients with selective IgA deficiency (SIgAD), we observed that switched memory B cells are reduced due to the absence of IgA memory B cells. In agreement, IgA plasma cells are not generated in response to CpG. Unexpectedly, B cells from SIgAD patients show a reduced proliferative response to CD40L. Our results demonstrate that functional tests are an important tool to assess the functions of the humoral immune system.
authors: Division of Rheumatology, Ospedale Pediatrico Bambino Gesù IRCCS, Roma, Italy.
authors: Emiliano
authors: E
authors: Marasco
authors: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCSS, Roma, Italy.
authors: Chiara
authors: C
authors: Farroni
authors: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCSS, Roma, Italy.
authors: Simona
authors: S
authors: Cascioli
authors: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCSS, Roma, Italy.
authors: Valentina
authors: V
authors: Marcellini
authors: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCSS, Roma, Italy.
authors: Marco
authors: M
authors: Scarsella
authors: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCSS, Roma, Italy.
authors: Ezio
authors: E
authors: Giorda
authors: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCSS, Roma, Italy.
authors: Eva
authors: E
authors: Piano Mortari
authors: Department of Pediatrics, La Sapienza University of Rome, Rome, Italy.
authors: Lucia
authors: L
authors: Leonardi
authors: University Department of Pediatrics, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, University of Rome "Tor Vergata", Rome, Italy.
authors: Alessia
authors: A
authors: Scarselli
authors: Pediatric and Infectious Disease Unit, Bambino Gesù Children's Hospital IRCCS, Rome, Italy.
authors: Diletta
authors: D
authors: Valentini
authors: University Department of Pediatrics, Unit of Immune and Infectious Diseases, Bambino Gesù Children's Hospital, University of Rome "Tor Vergata", Rome, Italy.
authors: Caterina
authors: C
authors: Cancrini
authors: Department of Pediatrics, La Sapienza University of Rome, Rome, Italy.
authors: Marzia
authors: M
authors: Duse
authors: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCSS, Roma, Italy.|Department of Rheumatology and Inflammation Research, University of Gothenburg, Gothenburg, Sweden.
authors: Ola
authors: O
authors: Grimsholm
authors: B Cell Physiopathology Unit, Immunology Research Area, Ospedale Pediatrico Bambino Gesù IRCSS, Roma, Italy.
authors: Rita
authors: R
authors: Carsetti
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D016175:B-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism*; D015415:Biomarkers; D019013:CD40 Antigens / Q000378:metabolism; D023201:CD40 Ligand / Q000276:immunology*; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D006801:Humans; D007070:Immunoglobulin A / Q000097:blood / Q000276:immunology; D017578:Immunoglobulin Class Switching; D007075:Immunoglobulin M / Q000097:blood / Q000276:immunology; D007153:Immunologic Deficiency Syndromes / Q000097:blood / Q000276:immunology* / Q000378:metabolism*; D007156:Immunologic Memory; D016130:Immunophenotyping; D007223:Infant; D008213:Lymphocyte Activation / Q000276:immunology*; D009838:Oligodeoxyribonucleotides / Q000276:immunology*; D010641:Phenotype; D011485:Protein Binding; D011947:Receptors, Antigen, B-Cell / Q000378:metabolism; D055815:Young Adult
chemical_list: D015415:Biomarkers; D019013:CD40 Antigens; C513533:CpG ODN 2006; D007070:Immunoglobulin A; D007075:Immunoglobulin M; D009838:Oligodeoxyribonucleotides; D011947:Receptors, Antigen, B-Cell; D023201:CD40 Ligand
keywords: B cells; Functional tests; Immunodeficiency; Pediatric immunology; Selective IgA deficiency