B cells are critical for a functional immune system. Activation of B cells results in a series of biochemical and cellular changes that convert naïve B cells to plasma cells. Differentiated plasma cells help the body to defend against foreign entities through the production of antibodies. This antigen-specific antibody production by plasma cells has also been exploited for the development of targeted therapeutics for cancer and other immune disorders. While B cells play a protective role in the adaptive immune system, dysfunctional B cells can lead to life threatening immunological disorders. Due to the importance of B cells for human health, studying the process of B-cell activation and plasma cell differentiation is an important part of life science research and therapeutic antibody discovery and development. However, highly specific surface markers for identifying plasma B cells are limited which imposes a challenge for researchers who want to isolate, characterize, and use them for research. In this proof-of-concept study, we used VisionSort to generate morphology-based markers of differentiated plasma B cells. The approach described here has potential clinical applications for cell line development, antibody discovery, and the generation of B cell therapies.