Researchers identified CD21 (complement receptor 2) as a key initiator of pathogenic extrafollicular (EF) B cell differentiation in a TLR7-driven lupus mouse model. Using an adoptive transfer system into 564Igi autoimmune mice, they tracked naïve B cells developing into autoantibody-secreting cells (ASCs). CD21 downregulation preceded proliferation and was directly linked to EF ASC fate. TLR7 deficiency severely impaired ASC generation, confirming TLR7 as essential for tolerance breakdown. BCR repertoire analysis revealed rapid clonal selection toward self-reactivity. These findings position CD21 as a therapeutic target for suppressing autoreactive B cell responses in systemic lupus erythematosus (SLE).
