期刊
JOURNAL OF EXPERIMENTAL MEDICINE
卷 219, 期 9, 页码 -出版社
ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20220201
关键词
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资金
- Swedish Research Council [2018-03128]
- Swedish Cancer Foundation [19 0464]
- Swedish Childhood Cancer Fund [PR2018-0170, PR2020-0147, TJ2019-0098]
- King Gustav V's 80-year Foundation [SGI-2018-0510, FAI-2019-0618, FAI-2020-0706]
- Assar Gabrielsson's Foundation [FB19-66, FB20-83, FB21-104]
- Elisabeth Bollan Linden-stipendiet
- Wenner-Gren Foundations
- Reumatikerforbundet
- ALF
- Kungl Vetenskaps-och Vitterhets-Samhallet
- Adlerbertska stiftelsen
- Stiftelsen Apotekare Hedbergs fond for medicinsk forskning
- Stiftelsen Samariten
- Amlovs Stiftelser
- Lundgrens Stiftelse
- Goteborgsregionens Stiftelse for Reumatologisk Forskning
- Ingabritt och Arne Lundbergs Forskningsstiftelse
- German Research Foundation (Deutsche Forschungsgemeinschaft) [TRR130]
- Roche Innovation Center Zurich
A recent study revealed that CD38 is a novel member of the IgM-BCR coreceptor, associating with CD19 in resting B cells and with CD19 and IgM after BCR stimulation. Targeting CD38 with an antibody impairs B cell proliferation and survival, as well as the formation of IgM:CD19 synapses.
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 alpha-CD38 antibodies could be a valuable option in therapeutic approaches to B cell malignancies driven by aberrant BCR signaling. This study shows that CD38 is a new member of the IgM-BCR coreceptor; it associates with CD19 in unstimulated B cells and with CD19 and IgM after BCR stimulation. Targeting CD38 with an antibody impairs B cell proliferation and survival, and formation of IgM:CD19 synapses.
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