Multiple immune tolerance mechanisms ensure that B or T cells carrying self-reactive receptors are either purged during development or inactivated in the periphery. How these self-reactive “rogue” lymphocyte clones break tolerance mechanisms and drive disease in autoimmune disorders is poorly understood. The recent emergence of single-cell technologies offers a powerful way to profile rogue cells within highly dynamic and heterogeneous immune populations. We present a computational pipeline to assemble full-length heavy and light chain BCR sequences and link this with the simultaneous measurement of transcriptional profiles and genomic variation of single B cells. We applied our approach to an Sjögren’s syndrome patient presenting IGHV1-69 IgM Rheumatoid Factor autoantibodies and an expanded IGHV1-69+ memory B cell population that persisted longitudinally. Single-cell RNA-sequencing followed by BCR assembly of IGHV1-69+ memory B cells revealed identical V, J and D segments and two extremely similar CDR3 sequences within each heavy and light chain. Transcriptome profiling coupled with surface phenotype markers additionally revealed that IGHV1-69+ memory B cells have a distinct phenotype when compared to clonally unrelated cells. We next performed targeted capture sequencing of cancer-driver genes of genomic DNA extracted and amplified from the same cells to identify a somatic point mutation in KLHL6, a predicted oncogene involved in BCR signalling. This exact mutation has been previously reported in both diffuse large B-cell lymphoma and chronic lymphoid leukemia and may thus contribute to disease pathogenesis. Finally, we present a method to sequence the paired antigen receptors of thousands of single B or T cells and link this to the gene expression profile of each cell. Overall, our results show that single-cell multi-omic technologies can be used to characterise a pathogenic B cell clone in an autoimmune disease patient and have the potential to transform our understanding of the complexity of autoimmune disease pathogenesis.