Glutamic acid decarboxylase 65-specific B-cell receptor (GAD65-BCR)

Glutamic acid decarboxylase 65-specific B-cell receptors (GAD65-BCRs) are membrane-bound immunoglobulins on B lymphocytes that selectively bind to the 65 kDa isoform of the enzyme glutamic acid decarboxylase (GAD65) (Baekkeskov et al., 1990). GAD65 is a critical autoantigen in Type 1 Diabetes (T1D) and Stiff Person Syndrome (SPS), where these specific B cells play a dual role by producing autoantibodies and acting as potent antigen-presenting cells that activate autoreactive T cells (Falcone et al., 1998; Solimena et al., 1988). In T1D, the interaction between GAD65 and its specific BCR facilitates the uptake and presentation of GAD65 peptides to CD4+ T cells, accelerating the destruction of insulin-producing beta cells in the pancreas (Smith et al., 2020). Therapeutic interventions targeting GAD65-BCRs, such as GAD-alum (Diamyd), aim to induce immunological tolerance or selectively modulate the autoreactive B-cell population to preserve beta-cell function (Ludvigsson et al., 2012). Unlike broad immunosuppressants, targeting GAD65-specific B cells offers a precision medicine approach to halt autoimmune progression while maintaining overall immune competence (Lernmark & Larsson, 2013). Research is also exploring the use of engineered cell therapies and tolerogenic vaccines to specifically silence these autoreactive clones (Smith et al., 2020).

Other names

GAD65-specific BCRGAD65-reactive B-cell receptorAnti-GAD65 B-cell receptorGAD65-specific immunoglobulin

Induction of antigen-specific immune tolerance to preserve pancreatic beta-cell function.