Antibodies generated by the humoral arm of the adaptive immune system play a crucial role in fighting disease and can be elicited by immunization with a vaccine or antigen displaying components of a disease-causing agent. Identification of these protective, antigen-specific antibody sequences enables their production and administration as therapeutically-relevant monoclonal antibodies. Glycan structures composed of carbohydrates are found on the surface of pathogenic bacteria, viruses, and tumor cells making them compelling antibody targets. However, glycans often elicit weak responses that generate suboptimal antibodies not suitable for monoclonal antibody therapy. Furthermore, current approaches for isolating antibody sequences are time-consuming and rely on large-scale screening methods adding to the challenges faced in anti-glycan antibody discovery. In this work we leverage recent technological advances, especially in designer immune tissue culture and next-generation sequencing, to improve upon the antigen immunization – antibody response – antibody discovery pipeline. First, we show that designer immune tissue organoids recapitulate key features of the in vivo immune response and can be used to characterize differences in the B cell response to different glycan-containing antigens. We further demonstrate that these organoids can be used to identify antigen-specific antibodies. We then utilize next-generation sequencing in lieu of traditional screening methods to analyze the antibody repertoire generated by immunization with glycoconjugate vaccines and show that anti-glycan antibodies are not immunodominant in these responses. Finally, we systematically construct minimal glycopeptide antigens in a modular fashion to allow for focusing of the antibody repertoire to the glycan targets of interest and enable antibody discovery by a high-throughput sequencing approach. With integration of these methods we envision a complete, quick, synthetic antibody discovery pipeline: rationally designed glyco-antigens synthesized to treat organoid immune tissues to generate glycan-specific B cells that are identified via high-throughput sequencing.