A Protease-Dependent Mechanism for Initiating T-Dependent B Cell Responses to Large Particulate Antigens

Antibody production is critical for antimicrobial immunity, and the initial step in this process is the binding of antigen to the B cell receptor. It has been shown that small soluble proteins can directly access the lymph node follicles to reach naïve B cells, but virus particles must be translocated into follicles via subcapsular sinus macrophages. Here, we explore how large particulate antigens generate humoral immune responses. Antigen-specific follicular B cells rapidly acquired antigen, presented peptide:MHC II ligands, and produced T-dependent antibody responses following subcutaneous injection of 1 µm, antigen-linked microspheres, despite the microspheres being confined to the subcapsular sinus. The mechanism of antigen acquisition did not require dendritic cells, subcapsular sinus macrophages, or B cell movement to the subcapsular sinus. Rather, B cell antigen acquisition was protease-dependent, suggesting that some protein antigens are cleaved from the surface of particles to directly initiate humoral immune responses