Membrane immunoglobulin M (mIgM)

Membrane immunoglobulin M (mIgM) is the antigen-binding subunit of the B-cell receptor (BCR) complex, primarily expressed on the surface of mature, naive B cells (UniProt P01871). It is composed of two mu heavy chains and two light chains, which are non-covalently associated with the CD79A and CD79B signaling heterodimer (StatPearls NBK559041). Upon antigen binding, mIgM undergoes conformational changes that initiate a complex intracellular signaling cascade involving kinases such as SYK, Lyn, and BTK, which are essential for B-cell survival, proliferation, and differentiation (Burger & Wiestner, 2018). In many B-cell malignancies, including chronic lymphocytic leukemia (CLL) and various non-Hodgkin lymphomas, the BCR signaling pathway is often constitutively active or hypersensitive, providing critical survival signals to malignant cells (PubMed: 29351928). Consequently, mIgM and its associated signaling network are major therapeutic targets in hematology. Drugs that inhibit downstream components of the mIgM-mediated signaling pathway, such as BTK inhibitors (e.g., Ibrutinib), have become standard of care for several B-cell cancers (NIH: NCATS). Additionally, mIgM expression levels and its signaling integrity are used as diagnostic and prognostic markers in clinical practice.

Other names

Surface IgMsIgMBCR-IgMImmunoglobulin heavy constant mu (membrane-bound)IGHMB-cell receptor complex (IgM-containing)

Inhibition of B-cell receptor (BCR) signaling pathway through the targeting of downstream kinases (e.g., BTK, SYK) or direct modulation of the receptor complex.