B cells biology in systemic lupus erythematosus—from bench to bedside

Abstract

Systemic lupus erythematosus (SLE) is a debilitating autoimmune disease that can involve multi-organs. B cells play a central role in the immunopathogenesis via antibody-dependent and antibody-independent ways. Excessive autoantibodies production, hyperresponsiveness and prolonged survival of autoreactive B cells are characteristics of SLE. In this article, mechanisms of self-tolerance loss of B cells and promising B cell-targeting therapies in lupus are reviewed and discussed. Systemic lupus erythematosus (SLE), the paradigm of autoimmune disease with the underlying mechanisms involving multiple immunological abnormalities, is a severely debilitating disease with multi-organ involvement and diverse autoantibodies spectrum [1]. Among the multiple elements in the pathogenesis, B cells play a central role in SLE through antibody dependent and independent manners [2]. Presence of pathogenic autoantibodies is not only the hallmark of SLE and the clue for diagnosis, but also associated with characteristic pathological injury and specific clinical manifestations [3][4][5]. In addition, the pathogenic role of B cells is also attributed to its antibody independent functions, including but not limited to antigen presentation, T cell crosstalk, dendritic cells (DCs) recruitment, pro-inflammatory cytokine secretion. Why and how auto-reactive B cells in lupus lose self-tolerance, escape from central and peripheral checkpoints, become over-activated and spontaneously produce autoantibodies, are always the focus of clinical and basic research. Therefore, it is important to summarize our current knowledge about the underlying mechanisms of self-tolerance breakdown and pathogenic functioning pathways of B cells in SLE. So we review here about B cell biology in SLE, including its differentiation and selection, functioning and signaling, surviving and apoptosis, and the resulting potential therapeutic targets both in mice and human lupus.

CXCR4 and CXCR5 orchestrate dynamic germinal center reactions and may contribute to the pathogenesis of systemic lupus erythematosus

“…B cells play a central role in the pathogenesis of SLE as the precursors of autoantibody-secreting cells, powerful antigenpresenting cells and cytokine producers. 2 Although antibodysecreting cells (ASCs) could derive extrafollicularly, GC is believed to be the main site for generating long-lived plasma cells and memory B cells, which are overactivated in SLE and capable of producing pathogenic autoantibodies persistently. 3 In GC, B cells are subdued to affinity-driven evolution and selection, followed by clonal expansion or deletion.…”

Human Umbilical Cord Mesenchymal Stem Cells Suppress Systemic Lupus Erythematosus Lesions by Rebalancing CD4+/CD8+ Cell Population

“…Excessive autoantibodies production, hyperresponsiveness and prolonged survival of auto reactive B cells are characteristics of SLE [60]. These B cells-related characteristics were not identified, which is a limitation in present research.…”

CARs: a new approach for the treatment of autoimmune diseases

“…Similar approaches for whole-B-cell depletion are also being used to treat disorders such as myasthenia gravis (MG) and neuromyelitis optica spectrum disorders (NMOSDs). SLE: SLE is the prototypical systemic autoimmune disease, and it is characterized by many types of autoreactive B cells and high levels of autoantibodies (Zhao et al, 2015). Antibody therapies that target B cells are unsatisfactory, and responses vary among different patients (Vital et al, 2011).…”