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Transcriptional and epigenetic regulation of B cell development

  • University of Pittsburgh Immunology 2011
  • Published:
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Abstract

B cell development starts in the bone marrow where hematopoietic stem cells (HSCs) progress through sequential developmental stages, as it differentiates into a naïve B cell expressing surface immunoglobulin. In the periphery, B cells that encounter antigen can further differentiate into antibody-secreting plasma cells. In this review, we focus on two factors, E47 and ELL2, which play important roles in the regulation of B cell development in the bone marrow and differentiation of mature B cells into plasma cells in the periphery, respectively. First, E47 activity is required for B cell development in the bone marrow. In addition, we have identified a cell-intrinsic role for E47 in regulating efficient self-renewal and long-term multilineage bone marrow reconstitution potential of HSCs. Second, we explored the role of transcription elongation factors in the super elongation complex (SEC), including ELL2 (eleven-nineteen lysine-rich leukemia factor) in driving poly(A) site choice and plasma cell development. We found that elongation factors impel high levels of IgH mRNA production and alternative processing at the promoter proximal, secretory-specific (sec) poly(A) site in plasma cells by enhancing RNA polymerase II modifications and downstream events. The sec poly(A) site, essentially hidden in B cells, is found by SEC factors in plasma cells.

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Acknowledgments

We would like to thank Dewayne Falkner for help with the cell sorting. This work is supported by grant # MCB-0842725 from the National Science Foundation (CM), NIH ARO54529 (LB), AI079047 (LB).

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  1. Department of Immunology, University of Pittsburgh School of Medicine, 200 Lothrop Street, Pittsburgh, PA, 15261, USA

    Patricia Santos, Fortuna Arumemi, Kyung Soo Park, Lisa Borghesi & Christine Milcarek

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  1. Patricia Santos
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  2. Fortuna Arumemi
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  3. Kyung Soo Park
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  4. Lisa Borghesi
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  5. Christine Milcarek
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Correspondence to Lisa Borghesi or Christine Milcarek.

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Fortuna Arumemi is a co-first author of this article.

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Santos, P., Arumemi, F., Park, K.S. et al. Transcriptional and epigenetic regulation of B cell development. Immunol Res 50, 105–112 (2011). https://doi.org/10.1007/s12026-011-8225-y

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