What is the function of antisense intergenic transcription in V(D)J recombination?

Lead Research Organisation: Babraham Institute
Department Name: UNLISTED

Abstract

One of the ways in which the immune system fights infections is by using antibodies, which attack and remove the many foreign agents such as bacterial toxins that the body encounters. Since there are literally millions of different possible invading proteins that the immune system may have to deal with, B cells (a type of white blood cell ) have evolved a way of making millions of different antibodies. They are made by cutting and pasting together one each of three different kinds of gene segments: V, D and J, to make an immunoglobulin protein. There are several D and J genes and 200 V genes, thus many different combinations can be made and this process, called V(D)J recombination, ensures that the immune system produces a sufficient diversity of antibodies to fight infection. The enormous DNA locus that contains all of these genes must be kept shut down in most cells to avoid chromosomal translocations that can cause cancerous B cell lymphomas. Equally it must be opened up efficiently in B cells to generate a diverse repertoire to avoid immunodeficiency. We have discovered that just before V(D)J recombination, RNA transcripts (encoded by DNA) that do not make proteins, are made through the large antibody DNA locus. The key aim of our work is to discover the function of this non-coding RNA transcription in V(D)J recombination. This will also contribute to our understanding of its role in the rest of the genome. We will achieve this by stopping this transcription (production of RNA) in cells that make antibodies, and determining the effect on V(D)J recombination and production of antibodies. This work will (i) help us to understand how B cells make antibodies and (ii) may also identify molecules or processes that are involved in human disease, such as immunodeficiency and lymphomas.

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