Autoreactive B-cell receptor (BCR) (BCR)

Autoreactive B-cell receptors (BCRs) are membrane-bound immunoglobulins that recognize self-antigens, playing a central role in the pathogenesis of autoimmune diseases and B-cell malignancies (Yurasov et al., 2005). The idiotype refers to the unique set of antigenic determinants within the variable region of the BCR, which is specific to a single B-cell clone (Kwak, 2010). In B-cell lymphomas, the idiotype acts as a tumor-specific neoantigen, as the entire malignancy is derived from a single clone expressing the same unique BCR (Schuster et al., 2011). Therapeutic strategies targeting these receptors include idiotype-based vaccines and anti-idiotype antibodies, which aim to selectively eliminate pathogenic B-cell clones while sparing the broader immune system (Pierpont et al., 2018). This high degree of specificity offers a significant advantage over broad B-cell depletion therapies by reducing the risk of general immunosuppression. However, challenges such as the low immunogenicity of idiotypes and the potential for clonal evolution through somatic hypermutation remain significant hurdles in clinical development.

Other names

Self-reactive B-cell receptorB-cell idiotypeTumor-specific idiotypeSurface immunoglobulin idiotype

Selective depletion of specific B-cell clones via active or passive targeting of the unique idiotype region of the B-cell receptor to induce antibody-dependent cellular cytotoxicity or apoptosis.