Clarifying role changes in the immune system

Different classes of antibodies produce different immune responses in the body. Antibodies produced by a B cell can change class through a process called class switch recombination (CSR). This requires double-stranded breakage of DNA in two distantly separated ‘switch regions’, followed by repair that excludes the DNA between the breaks.

Researchers determined that a ‘transcription elongation complex’ known as DSIF is involved in CSR, but the contributions of its two subunits, Spt4 and Spt5, remained unclear. Work led by Tasuku Honjo at Kyoto University, Japan, has now defined the roles of these subunits¹.

By reducing cellular levels of Spt4 and Spt5 separately and testing for markers of CSR steps, the researchers showed that both subunits are essential for CSR. However, while only Spt5 reduction affected DNA breakage, diminishing either Spt4 or Spt5 inhibited repair. Such a functional separation was unexpected for a bona fide elongation complex.

Their work showed that Spt5 indirectly regulates DNA break formation by maintaining histone H3K4me3, which in turn is postulated to recruit the cleavage complex. 

“Our data suggest that Spt4 and Spt5 can function independently to modulate various nodes of CSR,” says first author Andre Stanlie. “Future studies on chromatic-associated transcription elongation factors should give further insights into the mechanistic aspects of immunoglobulin class switching.”