Both Notch1 and its ligands in B cells promote antibody production

Zhu, Gaizhi; Wang, Xiaoqian; Xiao, He; Liu, Xiaoling; Fang, Ying; Zhai, Bing; Xu, Ruifang; Han, Gencheng; Chen, Guojiang; Hou, Chunmei; Shen, Beifen; Li, Yan; Ma, Ning; Wu, Haitao; Liu, Guangchao; Wang, Renxi

doi:10.1016/j.molimm.2017.08.021

Cited by 15 publications

(18 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Balb/c and CD19 cre mice have been previously described [16, 17]. The Floxed Stch (Stch f/f ) mice in a B6 background were generated by Shanghai Biomodel Organism Science & Technology Development Co.,Ltd.…”

Section: Methodsmentioning

confidence: 99%

Gm40600 suppressed SP 2/0 isograft tumor by reducing Blimp1 and Xbp1 proteins

Fang

Zhai

et al. 2019

BMC Cancer

Self Cite

View full text Add to dashboard Cite

Background Multiple myeloma (MM), characterized by cancerous proliferation of plasmablasts (PB) and plasma cells (PC), remains incurable in many patients. Differentially expressed molecules between MM PCs and healthy PCs have been explored in order to identify novel targets for treating MM. In the present study, we searched for novel MM therapeutic targets by comparing mRNA expression patterns between the Mus musculus myeloma plasmablast-like SP 2/0 cell line and LPS-induced PB/PC. Methods Gene expression profiles of LPS-induced PB/PC and SP 2/0 cells were determined using RNA-sequencing. A predicted gene (Gm40600) was found to be expressed at a low level in SP 2/0 cells. To study the role of Gm40600 in malignant PC, Gm40600 cDNA was cloned into a lentiviral vector (LV201) containing a puromycin selectable marker that was then transfected into SP 2/0 cells. Stable Gm40600-expressing SP 2/0 cells were selected using puromycin. The effect of Gm40600 on SP 2/0 cell proliferation, cell cycle/apoptosis, and tumor progression was assessed by cell counting kit-8 (CCK8), flow cytometry (FACS), and the SP 2/0 isograft mouse model, respectively. The effect of Gm40600 on mRNA and protein expression was evaluated by RNA-sequencing and western blotting, respectively. Results We found that SP 2/0 cells expressed lower level of Gm40600 mRNA as compared to LPS-induced PB/PC. Overexpression of Gm40600 significantly suppressed SP 2/0 cell proliferation and isograft tumor progression in an isograft mouse model by promoting apoptosis. In addition, Gm40600 overexpression suppressed transcription of the gene encoding Bcl2. Gm40600 overexpression also reduced the expression of PC-associated transcription factors Blimp1 and Xbp1, which promote transcription of the gene that encodes Bcl2. Conclusions Gm40600 reduced SP 2/0 cell proliferation and isograft tumor growth and progression by suppressing Blimp1 and Xbp1-mediated Bcl2 transcription to induce apoptosis. Thus, regulation of a human homolog of Gm40600, or associated factors, may be a potential therapeutic approach for treating MM. Electronic supplementary material The online version of this article (10.1186/s12885-019-5848-1) contains supplementary material, which is available to authorized users.

show abstract

Section: Methodsmentioning

confidence: 99%

Gm40600 suppressed SP 2/0 isograft tumor by reducing Blimp1 and Xbp1 proteins

Fang

Zhai

et al. 2019

BMC Cancer

Self Cite

View full text Add to dashboard Cite

show abstract

“…A NOTCH1 signaling pathway is essential for the development of the lymphoid T lineage in the thymus [ 15 ]. In the B cell lineage, the transmembrane NOTCH1 protein is involved in the maintenance of hematopoietic stem cells [ 16 ]. Usually, NOTCH1 is repressed by PAX5; however, aberrant expression of NOTCH1 interferes with the B lymphoid phenotype of neoplastic B cells in the classical Hodgkin lymphoma [ 11 , 17 ].…”

Section: Discussionmentioning

confidence: 99%

Variable Expression of Notch1 and Pax5 in Classical Hodgkin Lymphoma and Infection with Epstein–Barr in Pediatric Patients

et al. 2020

View full text Add to dashboard Cite

NOTCH1 and PAX5 participate in the proliferation and differentiation of B and T lymphocytes. Their expression can be modified by activation of NOTCH1, induced by the Epstein–Barr (EBV) viral proteins identified as LMP1 and LMP2. To identify whether PAX5, NOTCH1, and EBV latency genes participate in the oncogenic process of pediatric patients with classical Hodgkin lymphoma (cHL), the present study aimed to identify the variable expression of NOTCH1 among disease subtypes and to assess its effect on PAX5 expression. A total of 41 paraffin-embedded tissues from Mexican pediatric patients with cHL were analyzed. The expression of CD30, CD20, NOTCH1, PAX5, and LMP1 was evaluated by immunohistochemistry and immunofluorescence. EBV detection was performed by in situ hybridization. Out of all cases, 78% (32/41) of the cHL cases were EBV positive. NOTCH1 expression was detected in 78.1% (25/32) of EBV-positive cases, nodular sclerosis being the most frequent subtype (11/25, 44%). In cases where the expression of both genes was identified, double immunofluorescence assays were conducted, finding no colocalization. We found that Reed–Sternberg cells had aberrant expression compared to their cells of origin (B lymphocytes) due to the molecular mechanisms involved in the loss of expression of PAX5 and that the identification of NOTCH1 could be considered as a candidate diagnostic/prognostic marker and a therapeutic target in pediatric cHL.

show abstract

“…SP 2/0 cells (ATCC R CRL-1581) were purchased from ATCC (Rockville, MD, USA) and cultured in RPMI 1640 medium. B-cell purification and in vitro differentiation were previously described [45,46]. Briefly, splenic B220 + B cells were separated by B220 microbeads (Cat No.…”

Section: Cell Sorting and Culturementioning

confidence: 99%

The E3 ubiquitin ligase Itch deficiency promotes antigen‐driven B‐cell responses in mice

Fang

Zhai

et al. 2020

Eur J Immunol

Self Cite

View full text Add to dashboard Cite

Deficiency of Itch, an E3 ubiquitin ligase, usually induced severe systemic and progressive autoimmune disease. The Itch function is well studied in T cells but not in B cells. We hypothesize that B‐cell‐specific Itch deficiency promoted antigen‐induced B‐cell activation and antibody‐expressing plasma cell (PC) production. We found that unlike Itch KO, Itch cKO (CD19creItchf/f) mice did not demonstrated a significant increase in the sizes of spleens and LNs, antibody level, and base mutation of antibody gene. However, in line with the fact that Itch expression decreased in GC B cells, PCs, and plasmablast (PB)‐like SP 2/0 cells, Itch deficiency promoted B‐cell activation and antibody production induced by antigens including lipopolysaccharide (LPS) and sheep red blood cells (SRBCs). Mechanistically, we found that Itch deficiency promotes antigen‐induced cytokine production because Itch controls the proteins (e.g., eIF3a, eIF3c, eIF3h) with translation initiation factor activity. Altogether, our data suggest that Itch deficiency promotes antigen‐driven B‐cell response. This may provide hints for Itch‐targeted treatment of patients with autoimmune disease.

show abstract

Both Notch1 and its ligands in B cells promote antibody production

Cited by 15 publications

References 38 publications

Gm40600 suppressed SP 2/0 isograft tumor by reducing Blimp1 and Xbp1 proteins

Gm40600 suppressed SP 2/0 isograft tumor by reducing Blimp1 and Xbp1 proteins

Variable Expression of Notch1 and Pax5 in Classical Hodgkin Lymphoma and Infection with Epstein–Barr in Pediatric Patients

The E3 ubiquitin ligase Itch deficiency promotes antigen‐driven B‐cell responses in mice

Contact Info

Product

Resources

About