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Across autoimmune diseases, the dominant pathogenic compartment varies, ranging from precursor\u2010dependent states to tissue\u2010compartment inflammation and long\u2010lived plasma cell\u2013weighted autoantibody production. This review synthesizes the biological rationale for B\u2010cell\u2013axis targeting across oncology and autoimmunity and proposes a pathobiological framework spanning precursor\u2010dependent, compartment\u2010dominant, and long\u2010lived plasma cell\u2013weighted archetypes. We outline the mechanisms, lineage coverage, depletion depth, durability, and tolerability of CD20\u2010, CD19\u2010, CD38\u2010, and BCMA\u2010directed antibodies, bispecific T\u2010cell engagers, and chimeric antigen receptor (CAR) T cells, and map these modalities onto biologically defined autoimmune archetypes. 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We further review plasma cell\u2013directed and T\u2010cell\u2013engaging strategies for deep immune resets in refractory disease, while clarifying implications for trial design, long\u2010term safety, and implementation. 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