Our body protects us from infections by making specific antibodies against the pathogens—a Darwinian approach where the winners are rare, long-lasting B cells. When the body is under attack, T cells detect antigens and activate B cells in the lymph nodes and spleen. These B cells cluster together into germinal centers, where they rapidly proliferate and differentiate to cells that can produce antibodies, which then respond to antigens.
Antibodies are also routinely used as therapeutic agents to fight a range of disorders including blood cancers, breast cancer, asthma, arthritis, and transplant rejection. To date, the scientific community has relied on animal models to generate high-affinity antibodies—antibodies that bind quickly to antigens—and to fundamentally understand the complexities of germinal center immunology. While recent studies have uncovered crucial signals in this process, scientists are far from understanding the extracellular and intracellular factors that contribute to the exuberant pace of the germinal reaction and conversion to antibody-secreting cells.
Ankur Singh, Biomedical Engineering/Mechanical and Aerospace Engineering, is developing biomaterials to recapitulate the generation of high-affinity, antigen-specific antibodies ex vivo. This technology could enable more rapid development of antibodies for use in the treatment of various chronic diseases. Such tissue models can also be used to improve the mechanistic investigation into signaling and the epigenetic mechanisms that regulate germinal center B cells.
The findings will enable an immune organoid that is capable of controlling the rate and fate of B cell development into antibody-producing cells and will therefore significantly complement in vivo studies to advance therapeutic strategies and fundamental knowledge. NIH Award Number: 1R01AI132738-01A1