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B-lymphocyte-induced maturation protein1 up-regulates the expression of B-cell maturation antigen in mouse plasma cells

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Abstract

B-lymphocyte-induced maturation protein1(Blimp-1) and B-cell maturation antigen (BCMA) are essential factors in the development and survival of plasma cells. However, whether Blimp-1 could regulate the expression of BCMA is unknown. We found that the BCMA promoter region did not have typical “TATA” and “CAAT” box, but contained several potential binding sites of transcription factors, including the consensus sequences for Blimp-1, located in the “−31 to −21” and “−46 to −36” from the potential transcription initiation site of the mouse BCMA gene, respectively. Furthermore, induction of Blimp-1 over-expression significantly up-regulated the expression of BCMA and increased the BCMA promoter activity in mouse J558L plasma cells. In parallel, knockdown of Blimp-1 expression by the Blimp-1-specific shRNA significantly reduced the BCMA mRNA transcription and protein expression in J558L cells in vitro. Substitution mutation of the “−38 to −42” sequence, but not the “−23 to −27”, in the BCMA promoter abolished the regulatory effect of Blimp-1 on the expression of BCMA. Importantly, Blimp-1 bound to the “GAAAC”, but not its mutant “GATTC”, contained BCMA promoter, as determined by competitive electrophoretic mobility shift assay (EMSA). Therefore, our data clearly suggest that Blimp-s a positive regulator of the expression of BCMA gene in mouse plasma cells.

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Abbreviations

Blimp-1:

B-lymphocyte-induced maturation protein1

BCMA:

B-cell maturation antigen

PCR:

Polymerase chain reaction

RT-PCR:

Reverse-transcripted polymerase Chain reaction

AMV:

Avian myeloblastosis virus

GAPDH:

Glyceraldehyde-3-phosphate dehydrogenase

MM:

Multiple myeloma

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Acknowledgments

The authors would like to thank Prof. Parijs LV from MIT, USA for his provision of the lentiviral vector pLL3.7, and Prof. Wei Sun for his help in preparing the manuscript. This study was supported by the grants from the National Natural Science Foundation of China (30972728), Natural Science Foundation Project of CQ CSTC (2007BB5076), and a grant from the Third Military Medical University, Chongqing, China.

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Authors and Affiliations

  1. Department of Clinical Laboratory, Third Affiliated Hospital of Third Military Medical University, Chongqing, 400042, China

    Shaoli Deng

  2. Department of Hepatobiliary Surgery, Third Affiliated Hospital of Third Military Medical University, Chongqing, 400042, China

    Tao Yuan

  3. Chinese PLA General Hospital, 2nd Affiliated Hospital, Beijing, 100091, China

    Xiaoxing Cheng

  4. Department of Microbiology, Third Military Medical University, Chongqing, 400042, China

    Rui Jian & Jing Jiang

Authors
  1. Shaoli Deng
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  2. Tao Yuan
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  3. Xiaoxing Cheng
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  4. Rui Jian
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  5. Jing Jiang
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Corresponding author

Correspondence to Shaoli Deng.

Additional information

Shaoli Deng and Tao Yuan contributed equally to this study.

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11033_2010_28_MOESM1_ESM.docx

Supplementary material 1 (Figure S1. Analysis of the 5′-upstream sequence of the mouse BCMA gene. The regulatory sites and elements in the 5′-end (−820 to +145) of the BCMA gene were analyzed using the softwares indicated in the method section. The specific region cloned into the luciferase reporter vector was underlined. The potential binding sequences of transcription factors were individually boxed and the specific transcription factors were marked on the top of the box. The potential TSS and translation initiation were highlighted. (Cutoff score = 85))

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Deng, S., Yuan, T., Cheng, X. et al. B-lymphocyte-induced maturation protein1 up-regulates the expression of B-cell maturation antigen in mouse plasma cells. Mol Biol Rep 37, 3747–3755 (2010). https://doi.org/10.1007/s11033-010-0028-z

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  • DOI: https://doi.org/10.1007/s11033-010-0028-z

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