IgA class switch in I alpha exon-deficient mice. Role of germline transcription in class switch recombination.

IgA class switch in I alpha exon-deficient mice. Role of germline transcription in class switch recombination.

Studies have implicated defective Ig class switch in the pathogenesis of IgA deficiency. To understand better the molecular events that regulate IgA class switch, a 1.4-kb region of the IgA locus containing the I alpha exon was replaced with a human hypoxanthine phosphoribosyltransferase minigene by gene targeting in murine embryonic stem cells. The I alpha exon-deficient mice derived from thes...

Immunoglobulin Class Switch Recombination Is Impaired in Atm-deficient Mice

Immunoglobulin class switch recombination (Ig CSR) involves DNA double strand breaks (DSBs) at recombining switch regions and repair of these breaks by nonhomologous end-joining. Because the protein kinase ataxia telengiectasia (AT) mutated (ATM) plays a critical role in DSB repair and AT patients show abnormalities of Ig isotype expression, we assessed the role of ATM in CSR by examining ATM-d...

Quantitative Regulation of Class Switch Recombination by Switch Region Transcription

The isotype specificity of immunoglobulin (Ig) class switching is regulated by a cytokine which induces transcription of a specific switch (S) region, giving rise to so-called germline transcripts. Although previous studies have demonstrated that germline transcription of an S region is required for class switch recombination (CSR) of that particular S region, it has not been shown whether the ...

Switch Recombination in Cytokine-Induced Gene-Specific Class The Role of Germline Promoters and I Exons

The role of germline promoters and I exons in cytokine-induced gene-specific class switch recombination.

Germline transcription precedes class switch recombination (CSR). The promoter regions and I exons of these germline transcripts include binding sites for activation- and cytokine-induced transcription factors, and the promoter regions/I exons are essential for CSR. Therefore, it is a strong hypothesis that the promoter/I exons regions are responsible for much of cytokine-regulated, gene-specif...