Disease-specific autoantibody-producing B cell

Disease-specific autoantibody-producing B cells are a specialized subset of the B-lymphocyte lineage that have escaped immune tolerance mechanisms to produce immunoglobulins directed against self-antigens (Ellebrecht et al., 2016). These cells are the primary drivers of antibody-mediated autoimmune diseases, such as Pemphigus Vulgaris, Myasthenia Gravis, and Systemic Lupus Erythematosus, where they secrete pathogenic autoantibodies that cause tissue damage or functional interference (Lee et al., 2021). Beyond antibody production, these B cells contribute to disease by acting as professional antigen-presenting cells that activate autoreactive T cells and by secreting pro-inflammatory cytokines (Payne et al., 2019). While traditional therapies like Rituximab or Inebilizumab achieve therapeutic effects through broad depletion of B-cell populations via markers like CD20 or CD19, they often lead to significant side effects such as hypogammaglobulinemia and increased infection risk (Lee et al., 2021). Modern precision medicine approaches, such as Chimeric Autoantibody Receptor T-cell (CAAR-T) therapy, are designed to selectively target and eliminate only these disease-specific B cells by expressing the autoantigen on the T-cell surface to engage the specific B-cell receptor (Ellebrecht et al., 2016). This selective targeting aims to provide a curative approach for autoimmune diseases while preserving the rest of the healthy B-cell repertoire and maintaining overall humoral immunity (Payne et al., 2019). Although listed as a target, this entry refers to a heterogeneous cell population rather than a single molecular entity, which may be considered too much information or not a specific molecular target in traditional pharmacological databases.

Other names

Autoreactive B cellsPathogenic B cellsAutoantibody-secreting cellsSelf-reactive B lymphocytesPathogenic B-cell subsets

Mechanisms include broad B-cell depletion via antibody-dependent cellular cytotoxicity (ADCC) and complement-dependent cytotoxicity (CDC) targeting surface markers like CD20 or CD19, inhibition of B-cell survival factors such as BAFF/BLyS, and selective cellular cytotoxicity using Chimeric Autoantibody Receptor (CAAR) T-cells that recognize the specific B-cell receptor (BCR) of autoreactive cells (Lee et al., 2021; Ellebrecht et al., 2016).