TY - JOUR
T1 - B cells from nuclear factor kB essential modulator deficient patients fail to differentiate to antibody secreting cells in response to TLR9 ligand
AU - Giardino, Giuliana
AU - Cirillo, Emilia
AU - Gallo, Vera
AU - Esposito, Tiziana
AU - Fusco, Francesca
AU - Conte, Matilde Immacolata
AU - Quinti, Isabella
AU - Ursini, Matilde Valeria
AU - Carsetti, Rita
AU - Pignata, Claudio
PY - 2015/12/1
Y1 - 2015/12/1
N2 - Hypohidrotic ectodermal dysplasia (HED) consists of disorders resulting from molecular alterations of ectodysplasin-A (EDA) pathway. Hypomorphic mutations in NF-kB essential modulator, downstream EDA, result in HED with immunodeficiency (HED-ID), characterized by susceptibility to encapsulated pyogenic bacteria infections. Increased susceptibility to pneumococcal infections and poor response to polysaccharide antigens are associated with defect in T-independent B-cell immunity. We investigated B-cell differentiation and immunoglobulin secretion induced by the TLR9 ligand CpG in two HED-ID and in a HED patient caused by EDA mutations (XLHED). In HED-ID, only few B cells differentiated into plasma cells upon TLR9 stimulation and memory B cells did not produce IgG and IgA, but small amounts of IgM. Unexpectedly, memory B cells from XLHED patient failed to produce normal IgA or IgG amount upon TLR9 stimulation. Our findings expand the knowledge about the pathogenesis of humoral alterations in HED patients and help explain the susceptibility to pneumococcal infections.
AB - Hypohidrotic ectodermal dysplasia (HED) consists of disorders resulting from molecular alterations of ectodysplasin-A (EDA) pathway. Hypomorphic mutations in NF-kB essential modulator, downstream EDA, result in HED with immunodeficiency (HED-ID), characterized by susceptibility to encapsulated pyogenic bacteria infections. Increased susceptibility to pneumococcal infections and poor response to polysaccharide antigens are associated with defect in T-independent B-cell immunity. We investigated B-cell differentiation and immunoglobulin secretion induced by the TLR9 ligand CpG in two HED-ID and in a HED patient caused by EDA mutations (XLHED). In HED-ID, only few B cells differentiated into plasma cells upon TLR9 stimulation and memory B cells did not produce IgG and IgA, but small amounts of IgM. Unexpectedly, memory B cells from XLHED patient failed to produce normal IgA or IgG amount upon TLR9 stimulation. Our findings expand the knowledge about the pathogenesis of humoral alterations in HED patients and help explain the susceptibility to pneumococcal infections.
KW - CpG
KW - Encapsulated bacteria
KW - IgM memory B cell
KW - NEMO
KW - Nuclear factor kB essential modulator
KW - TLR9
UR - http://www.scopus.com/inward/record.url?scp=84942510596&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84942510596&partnerID=8YFLogxK
U2 - 10.1016/j.clim.2015.08.008
DO - 10.1016/j.clim.2015.08.008
M3 - Article
C2 - 26307434
AN - SCOPUS:84942510596
VL - 161
SP - 131
EP - 135
JO - Clinical Immunology
JF - Clinical Immunology
SN - 1521-6616
IS - 2
ER -