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

TL;DR

This paper reviews free light chains from B cells and non-B cells, highlighting their roles in health and disease, and their potential for new diagnostics and therapies.

Contribution

The paper introduces the novel concept of non-B cell-derived free light chains and their clinical significance.

Findings

Non-B cell-derived free light chains originate from epithelial and carcinoma cells.

Free light chains serve as biomarkers for multiple myeloma, amyloidosis, and renal injuries.

Differences in genetic and functional properties between B and non-B cell-derived FLCs are clinically relevant.

Abstract

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.

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