Genome-wide association studies (GWAS) have discovered tens of 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 therefore their contribution to disease pathology. Recent studies have highlighted that many autoimmune risk loci show specific regulatory potential in germinal center B cells [1]. To explore this, we have annotated statistically fine-mapped GWAS risk loci (spanning 21 different autoimmune diseases) with human germinal center B cell ChIP-seq datasets (H3K27ac, H3K4me3, H3K4me1) and ATAC-seq to prioritise risk loci that are active in this cell type. Next, we have developed a high-throughput screening method to test the function of autoimmune risk loci by targeting them via CRISPR activation (CRISPRa). Given that transduction of primary immune cells is extremely difficult, we have optimized protocols for simultaneous viral delivery of several vectors required for CRISPRa into human B cells. We validated our approach by efficiently upregulating the expression of multiple target genes either by activating their promoters or non-coding regions that were predicted to be associated with those genes. Coupling CRISPRa with single-cell RNA-seq allowed us to identify novel gene targets for multiple non-coding regions linked to autoimmunity. Furthermore, we identified functional genetic variants for some of these regions using massive parallel reporter assays (MPRA). The application of pooled CRISPR activation screening coupled with single-cell RNA-seq in primary human germinal center B cells, for the first time, allows us to target regions containing genetic variants associated with autoimmunity and identify their downstream regulatory gene targets in a highly relevant cellular context for autoimmune disease development.