Researchers have uncovered a key step the body takes in starting up the process of antibody production and keeping it going. The scientists believe that by blocking or activating this pathway, they may someday be able to develop treatments for autoimmune disorders or create better vaccines. The study was done by scientists at the Medical College of Georgia at Augusta University and published in Nature Communications.
The pathway in question is called ufmylation. In this pathway, a polypeptide called Ufm1 targets other proteins, connecting with them and changing their function. One of these proteins is Ufbp1. In the current study, Ufbp1 was found to play a key role in differentiation of naïve B cells into antibody-producing plasma cells and for plasma cells to step up production of protective antibodies.
The way that Ufbp1 performs its task is by suppressing the enzyme PERK to assisst B cells differentiatiation. PERK responds to improperly folded proteins to try to get them back in order. When newly made proteins fold improperly, PERK gets activated, stopping new protein production and decreasing misfolded protein pileup. However, in order to ensure ample production of plasma cells, PERK is suppressed by Ufbp1.
They found that Ufbp1 gets upregulated in plasma cells so that the endoplasmic reticulum can expand and with it, the protein folding capacity. Ufbp1 deficiency in the plasma cells impairs expansion of the endoplasmic reticulum and antibody production.
"We knew that proteins were folded in the endoplasmic reticulum and that an expanded endoplasmic reticulum is the hallmark of secretory cells like plasma cells being made," said Dr. Nagendra Singh, immunologist in the Department of Biochemistry and Molecular Biology at the Medical College of Georgia at Augusta University, "but exactly what components were involved, we did not know."
The researchers hope to leverage this knowledge for a number of clinical applications. These findings could help in designing vaccines that more effectively prime B cells to remember potential invaders. The findings also could have applications in designing treatments for autoimmune diseases like lupus and arthritis where antibody production runs amok. Currently, the researchers are doing research in a mouse model of lupus to see if they’re able to make adjustments to the disease.