Ascorbic Acid‐derived New Polymer Spheres via Ternary Copolymerization for Highly Effective Activation of B Cells

Abstract Lymphocytes are crucial to defend against harmful pathogens and sustain adaptive immunity. Developing immunomodulating materials to activate lymphocytes is imperative to induce effective and enduring immune responses. Here, a new polymer serving as a highly efficient activator of B cells is reported and corresponding polymer spheres are synthesized through a droplet‐assisted ternary copolymerization process of ascorbic acid, ethylenediamine, and glyoxal. In‐depth studies are conducted on the polymerization mechanisms and polymer spheres ranging from 250 to 1200 nm with various surface functional groups are synthesized. These prepared polymer materials exhibit remarkable immunomodulatory functions correlated to the polymer spheres' size and surface functional groups, and effective activations on B cells are observed in vivo and in vitro. Through cell phagocytosis experiments and RNA sequencing analysis, it is proposed that the selective phagocytosis of B cells and the presence of CD21 on the B cell membrane contribute to the activation of B cells. This work has extended the realm of immunological research from a unique perspective of chemical synthesis, further substantiating the fundamental research and application potential of designing immunomodulating polymers.