How plasma cells differentiate

When the presence of an infectious threat puts the immune system on alert, B cells can respond by developing into plasma cells that secrete antibodies that bind the invading pathogen. This process is facilitated in part by Blimp-1, a protein that switches off genes that promote cell division and directs B cell on the path to differentiation.

The Blimp-1 protein can be modified by enzymatic linkage to a tiny protein called SUMO. New work from Kuo-I Lin and colleagues at Taiwan’s Academia Sinica has revealed this process as a key step in plasma cell development¹. They identified the specific amino acid on Blimp-1 that is linked to SUMO upon B cell activation. Then, they determined that mutation of this residue effectively cripples the capacity of B cells to develop into plasma cells.

Lin and colleagues subsequently found that this mutant form of Blimp-1, K816R, is less capable of repressing its target genes. K816R still localizes to the same places in the cell and binds to the same DNA sites as its wild-type counterpart. However, the researchers learned that Blimp-1 seems to require SUMO modification in order to bind to another protein, HDAC-2, which in turn enables Blimp-1 to exert its repressive effects and drive plasma cell differentiation.