The TLR7Y264H gain-of-function mutant was found to drive aberrant survival of BCR-activated B cells and accumulation of ABCs and GC B cells, resulting in a lupus-like phenotype, associated with aberrant survival of pathogenic autoreactive B cells in a GC-independent manner, suggesting an extrafollicular origin. The gene discussed is BCR; the disease is systemic lupus erythematosus.