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Diversity of Antigen Receptors01:28

Diversity of Antigen Receptors

Antigen receptors are essential components of the immune system crucial in defending the body against foreign invaders. These receptors are present on the surface of B and T cells, enabling them to recognize antigens and mount an appropriate immune response.
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Differentiating Functional Roles of Gene Expression from Immune and Non-immune Cells in Mouse Colitis by Bone Marrow Transplantation
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Published on: October 1, 2012

Differential splicing across immune system lineages.

Ayla Ergun1, Graeme Doran, James C Costello

  • 1Division of Immunology, Department of Microbiology and Immunobiology, Harvard Medical School, Boston, MA 02115, USA.

Proceedings of the National Academy of Sciences of the United States of America
|August 13, 2013
PubMed
Summary
This summary is machine-generated.

Alternative splicing (AS) is widespread in immune cells, generating novel gene variants. AS patterns in lymphocytes often act as on/off switches, linked to cell differentiation and cycling.

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T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing
08:59

T and B Cell Receptor Immune Repertoire Analysis using Next-generation Sequencing

Published on: January 12, 2021

Area of Science:

  • Genomics
  • Molecular Biology
  • Immunology

Background:

  • Alternative splicing (AS) significantly expands the proteomic diversity of mammalian genomes.
  • Understanding AS regulation across diverse cell types is crucial for comprehending gene expression.
  • The Immunological Genome Project (ImmGen) provides a rich dataset for immune cell transcriptomics.

Purpose of the Study:

  • To map the landscape and variation of alternative splicing across immune cell lineages.
  • To identify novel AS isoforms and regulatory patterns within the immune system.
  • To investigate the relationship between AS and immune cell differentiation.

Main Methods:

  • Comprehensive analysis of RNA sequencing and microarray data from the ImmGen Consortium.
  • Identification and quantification of alternative splicing isoforms.
  • Clustering analysis of exon inclusion/exclusion patterns.
  • Computational prediction and experimental validation of splicing regulator-AS exon associations.

Main Results:

  • Alternative splicing is pervasive in T and B lymphocytes, with 60% of genes exhibiting frequent AS isoforms, including 7,599 previously unreported ones.
  • Distinct cell-specific AS events were observed, with differential exon skipping in 5% of coexpressed genes between B and T cells.
  • AS isoform distribution often followed an 'all or none' pattern, suggesting on/off switching.
  • Approximately 70% of AS exons followed a common pattern associated with lineage differentiation and cell cycling.
  • Specific AS events distinguished myeloid from lymphoid cells, and a connection between hnRPLL and Ptprc splicing was validated.

Conclusions:

  • Alternative splicing is a major source of gene and protein diversity in the mammalian immune system.
  • AS plays a significant role in immune cell lineage specification and differentiation.
  • Splicing regulators like hnRPLL are key players in orchestrating cell-specific AS events, exemplified by the Ptprc connection.