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B-cell activation with CD40L or CpG measures the function of B-cell subsets and identifies specific defects in immunodeficient patients

Artikel i vetenskaplig tidskrift
Författare E. Marasco
C. Farroni
S. Cascioli
V. Marcellini
M. Scarsella
E. Giorda
E. Piano Mortari
L. Leonardi
A. Scarselli
D. Valentini
C. Cancrini
M. Duse
Ola Grimsholm
R. Carsetti
Publicerad i Eur J Immunol
Volym 47
Nummer/häfte 1
Sidor 131-143
ISSN 0014-2980
Publiceringsår 2017
Publicerad vid Institutionen för medicin, avdelningen för reumatologi och inflammationsforskning
Sidor 131-143
Språk en
Länkar dx.doi.org/10.1002/eji.201646574
Ämnesord Adolescent, Adult, Age Factors, Antigens, CD40/metabolism, B-Lymphocyte Subsets/*immunology/*metabolism, Biomarkers, CD40 Ligand/*immunology, Cells, Cultured, Child, Child, Preschool, Humans, Immunoglobulin A/blood/immunology, Immunoglobulin Class Switching, Immunoglobulin M/blood/immunology, Immunologic Deficiency Syndromes/blood/*immunology/*metabolism, Immunologic Memory, Immunophenotyping, Infant, Lymphocyte Activation/*immunology, Oligodeoxyribonucleotides/*immunology, Phenotype, Protein Binding, Receptors, Antigen, B-Cell/metabolism, Young Adult, B cells, Functional tests, Immunodeficiency, Pediatric immunology, Selective IgA deficiency
Ämneskategorier Reumatologi och inflammation

Sammanfattning

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 naive 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.

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