Two studies, published in the journal Nature Immunology, highlight the crucial role of mutations in the Blimp1 gene in lymphoma development.
The work centers on plasma cells, or immune cells that develop from B-cells and are involved in producing antibodies against invading pathogens. B-cells — the origin of B-cell lymphomas — need to be activated by foreign antigens to start the process of becoming plasma cells. Some of these plasma cells migrate to the bone marrow and act as memory cells. If the body encounters the same pathogen again, they are ready to provide a swift immune response, a process involved in the working of vaccines.
The exact mechanisms by which plasma cells develop and how they function have eluded scientists. A research team led by Meinrad Busslinger, at the Research Institute of Molecular Pathology in Vienna, Austria, found that the gene Blimp1 is a key factor regulating genes that control both the development and function of plasma cells. Martina Minnich, the study’s first author, said in a press release: “We found that more than 50 percent of these genes are regulated by Blimp1. Therefore, this factor must be of vital importance for plasma cells. Furthermore, we were able to show for the first time that Blimp1 not only switches genes off but can also switch other genes on. This is an important discovery for the understanding of plasma cell development.”
Dr. Busslinger added, “It regulates their mobility and migration to the bone marrow. Blimp1 is also responsible for the enormous increase in size of the endoplasmic reticulum and the strong up-regulation of antibody production in plasma cells. Humoral immunity would not be possible without Blimp1.”
Complementing the Austrian study, Australian researchers under the lead of Stephen Nutt at the Walter and Eliza Hall Institute of Medical Research in Melbourne observed that while mature plasma cells survive without Blimp1, they cannot produce antibodies without the factor.
According to the release, mutations in Blimp1 have more far-reaching consequences than the workings of the immune system. “Mutations in the Blimp1 gene can block the further differentiation of B-cells, which contributes to the formation of malign B cell tumors known as lymphomas. Moreover, quiescent plasma cells can sometimes switch to uncontrolled cell growth and thus turn into plasma cell tumors or multiple myelomas,” it reported.