4.7 Article

Human CD38 regulates B cell antigen receptor dynamic organization in normal and malignant B cells

期刊

JOURNAL OF EXPERIMENTAL MEDICINE
卷 219, 期 9, 页码 -

出版社

ROCKEFELLER UNIV PRESS
DOI: 10.1084/jem.20220201

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资金

  1. Swedish Research Council [2018-03128]
  2. Swedish Cancer Foundation [19 0464]
  3. Swedish Childhood Cancer Fund [PR2018-0170, PR2020-0147, TJ2019-0098]
  4. King Gustav V's 80-year Foundation [SGI-2018-0510, FAI-2019-0618, FAI-2020-0706]
  5. Assar Gabrielsson's Foundation [FB19-66, FB20-83, FB21-104]
  6. Elisabeth Bollan Linden-stipendiet
  7. Wenner-Gren Foundations
  8. Reumatikerforbundet
  9. ALF
  10. Kungl Vetenskaps-och Vitterhets-Samhallet
  11. Adlerbertska stiftelsen
  12. Stiftelsen Apotekare Hedbergs fond for medicinsk forskning
  13. Stiftelsen Samariten
  14. Amlovs Stiftelser
  15. Lundgrens Stiftelse
  16. Goteborgsregionens Stiftelse for Reumatologisk Forskning
  17. Ingabritt och Arne Lundbergs Forskningsstiftelse
  18. German Research Foundation (Deutsche Forschungsgemeinschaft) [TRR130]
  19. Roche Innovation Center Zurich

向作者/读者索取更多资源

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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