B cells as under-appreciated mediators of non-auto-immune inflammatory disease

Abstract

B lymphocytes play roles in many autoimmune diseases characterized by unresolved inflammation, and B cell ablation is proving to be a relatively safe, effective treatment for such diseases. B cells function, in part, as important sources of regulatory cytokines in autoimmune disease, but B cell cytokines also play roles in other non-autoimmune inflammatory diseases. B cell ablation may therefore benefit inflammatory disease patients in addition to its demonstrated efficacy in autoimmune disease. Current ablation drugs clear both pro- and anti-inflammatory B cell subsets, which may unexpectedly exacerbate some pathologies. This possibility argues that a more thorough understanding of B cell function in human inflammatory disease is required to safely harness the clinical promise of B cell ablation. Type 2 diabetes (T2D) and periodontal disease (PD) are two inflammatory diseases characterized by little autoimmunity. These diseases are linked by coincident presentation and alterations in Toll-like receptor (TLR)-dependent B cell cytokine production, which may identify B cell ablation as a new therapy for co-affected individuals. Further analysis of the role B cells and B cell cytokines play in T2D, PD and other inflammatory diseases is required to justify testing B cell depletion therapies on a broader range of patients.

Characterization of Resident B Cells of Vascular Walls in Human Atherosclerotic Patients

“…B lymphocytes also formed a prominent part of the inflammatory cells in renal transplants (69) or kidney diseases (70). A fundamental pathogenic role for B cells was demonstrated in human diseases such as type 2 diabetes or periodontal disease (71) and in obesity-associated insulin resistance and glucose intolerance (72). Our results strongly suggest that B cells may be also important contributors to the physiopathology of human atherosclerosis.…”

Systemic toll-like receptor ligands modify B-cell responses in human inflammatory bowel disease

“…44 Our results suggest that systemic host (HMGB1) or microbial (such as PS-A) TLR2 and/or CD36 ligands may have a strong role in IBD pathogenesis through B cells that secrete high levels of inflammatory mediators. 23,45 In contrast, the role of systemic LPS is more complex and appears disease-specific.…”

Inflammaging decreases adaptive and innate immune responses in mice and humans

“…T2D is a metabolic, inflammatory disease not associated with autoimmunity, but often characterized by obesity, hypertension, dyslipidemia, accelerated atherosclerosis and increased mortality (Alberti and Zimmet 1998; Nikolajczyk 2010). We found that the in vivo responses, as well as B cell-specific markers identified above, decrease by age in healthy individuals but not in T2D patients, despite high levels of B cell-intrinsic inflammation measured by intracellular TNF-α in T2D patients.…”