Subtraction of sialic acids from glycans on the cell surface is important for communication between immune cells. Therefore, I hypothesized that there must be a sialidase that acts on immune cells in physiological conditions, that is, at neutral pH. Such a sialidase was examined using mouse immune tissues: the thymus, spleen and lymph node. We observed higher sialidase activity at neutral pH than acidic pH in the crude membrane fraction from the thymus but not in spleen or lymph node tissues. There is no such property among the four kinds of sialidases that have been cloned from vertebrates. We tried to clarify the true nature of the enzyme, and found NEU2-like sialidase-positive cells in the thymus histochemically using 5-bromo-4-chloro-3-indolyl-α-D-Nacetylneuraminic acid and named them Neu-medullocytes. Recently, we showed that Neu-medullocytes are CD5 positive B cells (B-1 cells), and some of them express the transcription factor autoimmune regulator (AIRE). Thus, the physiological function of these cells is probably to act as antigen-presenting cells that present carbohydrate antigens, as is characteristic of B-1 cells, during negative selection step in the thymus. The absence of autoantibodies against self-carbohydrate antigens such as blood type can be explained by the existence of these cells. © 2020 FCCA (Forum: Carbohydrates Coming of Age) E16 C. Several Points Remain Unsolved and Should be Clarified in the Future C-1. The True Enzyme of MSAN