B cells are important in the pathogenesis of many, and perhaps all, immune-mediated diseases. Here we describe methods that characterise the human adaptive immune response by high-throughput sequencing of B cell receptors and single cell transcriptomics. I will describe how we are using these technologies to understand the immune responses across health, autoimmune diseases, immunodeficiencies and cancer, and how we can leverage this knowledge gained across pathologies to direct us towards more targeted therapies.