2015
DOI: 10.1074/jbc.m114.618496
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Scaffold Protein JLP Is Critical for CD40 Signaling in B Lymphocytes

Abstract: Background:The roles of JLP in CD40 trafficking and signaling in B lymphocytes remain elusive. Results: JLP deficiency in B lymphocytes resulted in selective diminished CD40 internalization and activation of MAPK and JNK. Conclusion: JLP-mediated CD40 internalization is essential for downstream JNK and MAPK signaling in B lymphocytes. Significance: We report a novel role of JLP in the bridging of CD40 internalization and CD40-dependent signaling in B lymphocytes.

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Cited by 16 publications
(11 citation statements)
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“…[ 29 , 30 ] CD40 was initially found in B lymphocytes, which has been suggested to be participated in the activation of B cells and has other key roles. [ 31 ] Apoptosis induction can be inhibited by the interaction between CD40 and their ligands in B lymphocytes [ 32 ] ; but the expression level of CD40 is low under normal physiological conditions, which may be significantly up-regulated under pathological conditions. [ 33 ] Importantly, as the key hub of the inflammatory and immune responses in vivo, the CD40/CD40L system may be responsible for antigen presentation and immune response, and associate significantly with the activation of T lymphocytes and macrophages, thereby exerting critical biological roles in different cell types by the modulation of different signaling pathways.…”
Section: Discussionmentioning
confidence: 99%
“…[ 29 , 30 ] CD40 was initially found in B lymphocytes, which has been suggested to be participated in the activation of B cells and has other key roles. [ 31 ] Apoptosis induction can be inhibited by the interaction between CD40 and their ligands in B lymphocytes [ 32 ] ; but the expression level of CD40 is low under normal physiological conditions, which may be significantly up-regulated under pathological conditions. [ 33 ] Importantly, as the key hub of the inflammatory and immune responses in vivo, the CD40/CD40L system may be responsible for antigen presentation and immune response, and associate significantly with the activation of T lymphocytes and macrophages, thereby exerting critical biological roles in different cell types by the modulation of different signaling pathways.…”
Section: Discussionmentioning
confidence: 99%
“…CD40L binding to CD40 leads to CD40 internalization. Engagement of CD40 on murine B cells by sCD40L leads to rapid loss of surface CD40 expression by receptor internalization (16)(17)(18). To test whether CD40L expressed by B cells could engage CD40 on B cells and explain the phenotype observed in SLE African American patients, we cultured purified B cells from NHV with soluble CD40L-isoleucine zipper (CD40L-IZ) or anti-IgM F(ab') 2 .…”
Section: Cd45romentioning
confidence: 99%
“…The observed decrease in CD40 may seem paradoxical at first given that M-MDSCs also increased B cell production of class-switched Abs. However, this may be explained, at least in part, by the observation that in other systems, CD40 is internalized after ligation (73,74). We have previously published that CD40-CD154 binding between B and CD4 + T cells, respectively, and CD40 signaling through selective TRAF adaptor proteins is required for initiation and progression of LP-BM5-induced pathogenesis (49,(75)(76)(77).…”
Section: Discussionmentioning
confidence: 84%