B Cell-Derived and Non-B Cell-Derived Free Light Chains: From Generation to Biological and Pathophysiological Roles

Immunoglobulin light chains are essential components of intact immunoglobulins, traditionally believed to be produced exclusively by B cells. Physiologically, excess light chains not assembled into intact antibodies exist as free light chains (FLCs). Increasingly recognized as important biomarkers for diseases such as multiple myeloma, systemic amyloidosis, and light chain-related renal injuries, FLCs have also been shown in recent decades to originate from non-B cell sources, including epithelial and carcinoma cells. This review primarily focuses on novel non-B cell-derived FLCs, which challenge the conventional paradigms. It systematically compares B cell-derived and non-B cell-derived FLCs, analyzing differences in genetic features, physicochemical properties, and functional roles in both health and disease. By elucidating the distinctions and similarities in their nature as immune regulators and disease mediators, we highlight the significant clinical potential of FLCs, particularly non-B cell-derived FLCs, for novel diagnostic and therapeutic strategies.