Hide and Go Seek: Activation of the Secretory-Specific Poly (A) Site of Igh by Transcription Elongation Factors

Milcarek, Christine

doi:10.5772/21186

Cited by 4 publications

(1 citation statement)

References 177 publications

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“…The IgH transcripts of any isotype are subject to alternative RNA processing [39]. When the sec poly(A) site is used, the pre-mRNA is cleaved so that splicing between the site embedded in the last sec exon and M1 does not occur.…”

Section: A Requirement For E47 In Development and Maintenance Of Hscsmentioning

confidence: 99%

Transcriptional and epigenetic regulation of B cell development

et al. 2011

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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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Section: A Requirement For E47 In Development and Maintenance Of Hscsmentioning

confidence: 99%

Transcriptional and epigenetic regulation of B cell development

et al. 2011

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Genome Engineering of Hybridomas to Generate Stable Cell Lines for Antibody Expression

Parola

Mason

Zingg

et al. 2018

Methods in Molecular Biology

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Plasma cells require autophagy for sustainable immunoglobulin production

Pengo¹,

Scolari²,

Oliva³

et al. 2013

Nat Immunol

366

433

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The role of autophagy in plasma cells is unknown. Here we found notable autophagic activity in both differentiating and long-lived plasma cells and investigated its function through the use of mice with conditional deficiency in the essential autophagic molecule Atg5 in B cells. Atg5(-/-) differentiating plasma cells had a larger endoplasmic reticulum (ER) and more ER stress signaling than did their wild-type counterparts, which led to higher expression of the transcriptional repressor Blimp-1 and immunoglobulins and more antibody secretion. The enhanced immunoglobulin synthesis was associated with less intracellular ATP and more death of mutant plasma cells, which identified an unsuspected autophagy-dependent cytoprotective trade-off between immunoglobulin synthesis and viability. In vivo, mice with conditional deficiency in Atg5 in B cells had defective antibody responses, complete selection in the bone marrow for plasma cells that escaped Atg5 deletion and fewer antigen-specific long-lived bone marrow plasma cells than did wild-type mice, despite having normal germinal center responses. Thus, autophagy is specifically required for plasma cell homeostasis and long-lived humoral immunity.

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Hide and Go Seek: Activation of the Secretory-Specific Poly (A) Site of Igh by Transcription Elongation Factors

Cited by 4 publications

References 177 publications

Transcriptional and epigenetic regulation of B cell development

Transcriptional and epigenetic regulation of B cell development

Genome Engineering of Hybridomas to Generate Stable Cell Lines for Antibody Expression

Plasma cells require autophagy for sustainable immunoglobulin production

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