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

ABSTRACT: 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.

SUBMITTER: Camponeschi A

PROVIDER: S-EPMC9280193 | biostudies-literature | 2022 Sep

REPOSITORIES: biostudies-literature

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

Camponeschi Alessandro A Kläsener Kathrin K Sundell Timothy T Lundqvist Christina C Manna Paul T PT Ayoubzadeh Negar N Sundqvist Martina M Thorarinsdottir Katrin K Gatto Mariele M Visentini Marcella M Önnheim Karin K Aranburu Alaitz A Forsman Huamei H Ekwall Olov O Fogelstrand Linda L Gjertsson Inger I Reth Michael M Mårtensson Inga-Lill IL

The Journal of experimental medicine 20220712 9

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, inhibit ...[more]

PMID: 35819358

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Dataset Information

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

Publications

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

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