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B Cell Activation and Differentiation01:24

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The adaptive immune response, a sophisticated defense mechanism, relies on the activation and differentiation of B lymphocytes, or B cells. These processes enable our bodies to mount a tailored response against specific pathogens such as bacteria, free virus particles, toxins, and parasites.
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lncRNA - Long Non-coding RNAs02:39

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In humans, more than 80% of the genome gets transcribed. However, only around 2% of the genome codes for proteins. The remaining part produces non-coding RNAs which includes ribosomal RNAs, transfer RNAs, telomerase RNAs, and regulatory RNAs, among other types. A large number of regulatory non-coding RNAs have been classified into two groups depending upon their length – small non-coding RNAs, such as microRNA, which are less than 200 nucleotides in length, and long non-coding RNA...
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The T and B lymphocytes of the adaptive immune system develop from common lymphoid progenitor cells in the bone marrow. These progenitors give rise to precursors that eventually develop into both T and B lymphocytes. As these precursors mature, they gain the ability to detect and respond to foreign antigens in the body, a process known as immunocompetence. Additionally, these precursors acquire self-tolerance, a process that ensures they do not react to self-antigens. This intricate system...
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T cells are integral to our adaptive immune system, recognizing and effectively responding to foreign antigens. T cell activation and clonal selection are pivotal in orchestrating this immune response. This article elucidates these mechanisms, detailing the roles of cluster of differentiation (CD) markers, major histocompatibility complex (MHC) molecules, costimulatory signals, and the process of clonal selection.
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Epigenetics is the study of inherited changes in a cell's phenotype without changing the DNA sequences. It provides a form of memory for the differential gene expression pattern to maintain cell lineage, position-effect variegation, dosage compensation, and maintenance of chromatin structures such as telomeres and centromeres. For example, the structure and location of the centromere on chromosomes are epigenetically inherited. Its functionality is not dictated or ensured by the underlying...
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Genome-wide Analysis of HDAC Inhibitor-mediated Modulation of microRNAs and mRNAs in B Cells Induced to Undergo Class-switch DNA Recombination and Plasma Cell Differentiation
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Long noncoding RNAs in B-cell development and activation.

Tiago F Brazão1, Jethro S Johnson2, Jennifer Müller1

  • 1The Francis Crick Institute, London, United Kingdom;

Blood
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Summary

Researchers discovered 4516 long noncoding RNAs (lncRNAs) during B-cell development. Many of these novel lncRNAs are regulated by the key B-cell transcription factor PAX5, offering new insights into B-cell biology.

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Area of Science:

  • Immunology
  • Molecular Biology
  • Genomics

Background:

  • Long noncoding RNAs (lncRNAs) are increasingly recognized for their regulatory roles in cellular processes.
  • Their specific functions in B lymphocyte development and differentiation remain largely unexplored.

Purpose of the Study:

  • To comprehensively identify and characterize lncRNAs expressed during B-cell development and activation.
  • To investigate the regulatory roles of lncRNAs and their association with key B-cell transcription factors.

Main Methods:

  • RNA sequencing (RNA-seq) and de novo transcript assembly were employed to identify lncRNAs across 11 stages of B-cell development.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) was used to classify lncRNAs and assess transcription factor binding.
  • Comparative analysis with human lncRNAs identified orthologous transcripts.

Main Results:

  • A catalog of 4516 lncRNAs expressed during B-cell development and activation was generated, with most being novel discoveries.
  • 185 mouse lncRNAs with human orthologs were identified.
  • 126 enhancer RNAs (eRNAs) were identified, correlating with nearby coding genes and indicating active enhancers.
  • The transcription factor PAX5 was found to bind and regulate 109 lncRNAs in normal B cells and 184 lncRNAs in acute lymphoblastic leukemia.

Conclusions:

  • This study provides a comprehensive resource of lncRNAs involved in B-cell development and activation.
  • PAX5 plays a significant role in regulating lncRNA expression within the B-cell lineage.
  • The identified lncRNAs and their regulatory interactions offer potential targets for understanding B-cell differentiation and associated malignancies.