When our immune system encounters a new pathogen plasma cells are created that secrete antibodies to specifically prevent future infections, generating immunity to that particular disease.
Following infection or immunisation an immune response is mounted that creates transitory germinal centres in peripheral lymphoid organs. Within the germinal centres B cells develop and differentiate (link is external) into antibody-generating plasma cells and memory B cells that mediate and sustain protection against invading pathogens. These germinal centres act as rapid proto-typing facilities to improve the specificity of antibodies produced by plasma cells, so that they better recognise invading pathogens.
Our bone marrow acts as a long term storage facility for plasma cells, allowing them to continue to produce antibodies to protect against future infections, but not all plasma cells generated as part of an immune response make it to the bone marrow to be stored to fight future infections. Some perish in the blood stream after just a few days, and until now we have not understood what distinguishes between the cells that are preserved by the bone marrow and those passed over in the bloodstream.
A recent study (link is external) published in the Journal of Experimental Medicine addresses just this question, demonstrating that a transcription factor, c-Myb, is responsible for the migration of plasma cells to the bone marrow, preserving them for many years or even decades. The study shows that using a temporally induced c-Myb knock-out mouse, in which c-Myb was deleted at the T2 stage of B cell development, the plasma cells of these mice were unable to move into the bone marrow to provide long-term immunity.
Researchers discovered that if c-Myb was activated at some stage during an immune response then those plasma cells had the ability to migrate into the bone marrow in response to the chemotactic factor CXCL12. Activation of c-Myb within plasma cells during antigenic variation acts to signal that these cells produce high-quality antibody for preservation.
If we can increase our understanding of how c-Myb acts as a molecular switch in plasma cells to create long-term immunity, we could engineer the immune system to retain plasma cells effective for a range of infections. Malarial pathogens typically trigger only short-lived plasma cells, thus individuals can suffer repeated episodes of the same disease. Through manipulating c-Myb in these plasma cells an opportunity exists to create long-term immunity to such diseases. Although it is clear that c-Myb is essential in the generation of humoral immunity we still do not know what signals c-Myb production or which genes are activated by c-Myb.