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

被引：23

作者：

Camponeschi, Alessandro ^{[1
]}

Klasener, Kathrin ^{[2
,3
,4
]}

Sundell, Timothy ^{[1
]}

Lundqvist, Christina ^{[1
]}

Manna, Paul T. ^{[5
]}

Ayoubzadeh, Negar ^{[1
]}

Sundqvist, Martina ^{[1
]}

Thorarinsdottir, Katrin ^{[1
]}

Gatto, Mariele ^{[1
,6
]}

Visentini, Marcella ^{[7
]}

Onnheim, Karin ^{[1
]}

Aranburu, Alaitz ^{[1
]}

Forsman, Huamei ^{[1
]}

Ekwall, Olov ^{[1
,8
]}

Fogelstrand, Linda ^{[9
,10
]}

Gjertsson, Inger ^{[1
]}

Reth, Michael ^{[2
,3
,4
]}

Martensson, Inga-Lill ^{[1
]}

机构：

[1] Univ Gothenburg, Sahlgrenska Acad, Inst Med, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden

[2] Univ Freiburg, Fac Biol, Biol 3, Freiburg, Germany

[3] Univ Freiburg, Signalling Res Ctr Biol Signalling Studies, Freiburg, Germany

[4] Univ Freiburg, Ctr Integrat Biol Signalling Studies, Freiburg, Germany

[5] Univ Gothenburg, Sahlgrenska Acad, Inst Neurosci & Physiol, Dept Physiol, Gothenburg, Sweden

[6] Univ Padua, Dept Med, Unit Rheumatol, Padua, Italy

[7] Sapienza Univ Rome, Dept Translat & Precis Med, Rome, Italy

[8] Univ Gothenburg, Sahlgrenska Acad, Inst Clin Sci, Dept Pediat, Gothenburg, Sweden

[9] Univ Gothenburg, Sahlgrenska Acad, Inst Biomed, Dept Lab Med, Gothenburg, Sweden

[10] Sahlgrens Univ Hosp, Dept Clin Chem, Gothenburg, Sweden

来源：

JOURNAL OF EXPERIMENTAL MEDICINE | 2022年 / 219卷 / 09期

基金：

瑞典研究理事会;

关键词：

ADP-RIBOSYL CYCLASE; CD19; KINASE; FAMILY; ACTIVATION; MOLECULE;

D O I：

10.1084/jem.20220201

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页数：17

共 39 条

[11] CD19 function in central and peripheral B-cell development [J].