Considering that B cells rely on lysosomes for the extraction and processing of antigens, it is relevant to elucidate how lysosomes and lysosomal hydrolases such as cathepsins, respond to an excess of nutrients in obesity and LSDs, and how these signals crosstalk with the activation of B cells during antigen recognition. The gene discussed is CTSS; the disease is obesity due to melanocortin 4 receptor deficiency.