Significance Progress in understanding and treating inflammatory diseases relies on accurate characterization of the molecular pathology. From application of nanoparticle tracking analysis, we expose a fundamental insight in oligomeric protein structure as polyvalent stimulants of autoreactive B cells. Quantification of hydrodynamic radii implicates these large proteins as part of vascular damage, which is an important source of morbidity and death in consequence of autoimmunity. Dysregulated alterations in protein concentration have been often sought as an explanation for diseases. Our work highlights now protein size as a key parameter in the inflammatory response both in and outside lymphoid organs. In this way, our findings may have wide implications for understanding disease associations based on polymerization and hydrodynamic radius changes of biological macromolecules.