Human CD38 regulates B cell antigen receptor dynamic organization in normal and malignant B cells.
Journal
The Journal of experimental medicine
ISSN: 1540-9538
Titre abrégé: J Exp Med
Pays: United States
ID NLM: 2985109R
Informations de publication
Date de publication:
05 09 2022
05 09 2022
Historique:
received:
03
02
2022
revised:
11
05
2022
accepted:
13
06
2022
entrez:
12
7
2022
pubmed:
13
7
2022
medline:
15
7
2022
Statut:
ppublish
Résumé
CD38 is a multifunctional protein expressed on the surface of B cells in healthy individuals but also in B cell malignancies. Previous studies have suggested a connection between CD38 and components of the IgM class B cell antigen receptor (IgM-BCR) and its coreceptor complex. Here, we provide evidence that CD38 is closely associated with CD19 in resting B cells and with the IgM-BCR upon engagement. We show that targeting CD38 with an antibody, or removing this molecule with CRISPR/Cas9, inhibits the association of CD19 with the IgM-BCR, impairing BCR signaling in normal and malignant B cells. Together, our data suggest that CD38 is a new member of the BCR coreceptor complex, where it exerts a modulatory effect on B cell activation upon antigen recognition by regulating CD19. Our study also reveals a new mechanism where α-CD38 antibodies could be a valuable option in therapeutic approaches to B cell malignancies driven by aberrant BCR signaling.
Identifiants
pubmed: 35819358
pii: 213348
doi: 10.1084/jem.20220201
pmc: PMC9280193
pii:
doi:
Substances chimiques
Adaptor Proteins, Signal Transducing
0
Antigens, CD19
0
Immunoglobulin M
0
Membrane Glycoproteins
0
Receptors, Antigen, B-Cell
0
CD38 protein, human
EC 3.2.2.5
ADP-ribosyl Cyclase 1
EC 3.2.2.6
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : Swedish Research Council
ID : 2018-03128
Organisme : Swedish Cancer Foundation
ID : 19 0464
Organisme : Swedish Childhood Cancer Foundation
ID : PR2018-0170
Organisme : King Gustav V's 80-year Foundation
ID : SGI-2018-0510
Organisme : Elisabeth Bollan Lindén-stipendiet
Organisme : Assar Gabrielsson's Foundation
ID : FB19-66
Organisme : Wenner-Gren Foundation
Organisme : Reumatikerförbundet
Organisme : ALF
Organisme : Kungl. Vetenskaps- och Vitterhets-Samhället i Göteborg
Organisme : Adlerbertska Stiftelserna
Organisme : Stiftelsen Apotekare Hedbergs Fond för Medicinsk Forskning
Organisme : Stiftelsen Samariten
Organisme : German Research Foundation
ID : TRR130
Organisme : Roche Innovation Center Zurich
Organisme : Amlövs Stiftelser
Organisme : Lundgrens Stiftelse
Organisme : Göteborgsregionens Stiftelse för Reumatologisk Forskning
Organisme : Ingabritt och Arne Lundbergs Forskningsstiftelse
Informations de copyright
© 2022 Camponeschi et al.
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