Genome-wide association studies have discovered thousands of genetic variants associated with different autoimmune diseases, and yet the molecular pathways underlying these diseases have remained elusive. Over 90% of the identified genetic risk loci are in non-coding regions of the genome, which makes it challenging to predict the downstream gene regulatory consequences and their contribution to disease. Here, we have implemented a high-throughput screen to map the gene targets of autoimmune risk loci in germinal centre B cells - a highly relevant cellular context for autoimmune disease. Initially we prioritized 818 fine-mapped genetic variants from over 30 different autoimmune traits (including common conditions such as lupus, Crohn’s disease, and multiple sclerosis) located in non-coding genomic regions with high regulatory potential in human B cells. To test the function of these non-coding risk loci and identify their downstream target genes, we have coupled a CRISPR activation screen with single-cell RNA-seq and surface protein detection. This allowed us to quantify changes in both transcriptome and cell surface proteins resulting from the activation of hundreds of autoimmune risk loci in a single multiplexed experiment. Furthermore, we have for the first time quantified CRISPRa-dependent transcription of enhancer RNAs from autoimmune risk loci, further supporting their role in gene regulation. To date, this is the first single-cell CRISPR activation screen performed in primary human B cells and has quantified the regulatory effects of hundreds of autoimmune risk loci to experimentally identify their target genes. To determine how specific genetic variants at these autoimmune risk loci may control gene expression, we are conducting other experiments such as prime editing and massive parallel reporter assays. Ultimately, our goal is to understand the immune dysfunction in autoimmune disease and provide information needed to develop new therapeutics or diagnostics for patients with autoimmunity.