Membrane-bound immunoglobulin M (mIgM)

Membrane-bound immunoglobulin M (mIgM) is the antigen-binding subunit of the B-cell receptor (BCR) complex, primarily expressed on the surface of naive and memory B cells [1, 5]. It consists of two heavy chains (mu) and two light chains, anchored in the plasma membrane and non-covalently associated with the Ig-alpha/Ig-beta (CD79a/CD79b) signaling heterodimer [5, 40]. Upon antigen recognition, mIgM triggers intracellular signaling cascades involving kinases such as Syk and BTK, which are essential for B-cell activation, proliferation, and differentiation [1, 12]. In B-cell malignancies like chronic lymphocytic leukemia (CLL) and various lymphomas, mIgM-mediated signaling is often constitutively active, driving tumor survival and growth [1, 6]. Consequently, mIgM is a significant therapeutic target; drugs like the monoclonal antibody mAb4 are designed to bind unique epitopes on mIgM to inhibit BCR signaling and induce apoptosis [2, 29]. Unlike soluble IgM, mIgM contains a unique proximal domain that allows for highly specific targeting, potentially sparing normal tissues and reducing off-target effects [2, 8]. Therapeutic intervention targeting mIgM is also being explored for autoimmune diseases such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA) to modulate aberrant B-cell activity [1, 24].

Other names

Surface IgMmBCRMembrane IgMB-cell receptor component

Inhibition of B-cell receptor (BCR) signaling (e.g., dephosphorylation of BTK and Syk), induction of apoptosis, and receptor internalization [2, 29, 34].