Altered Germinal-Center Metabolism in B Cells in Autoimmunity

Abstract

B lymphocytes play an important role in the pathophysiology of many autoimmune disorders by producing autoantibodies, secreting cytokines, and presenting antigens. B cells undergo extreme physiological changes as they develop and differentiate. Aberrant function in tolerogenic checkpoints and the metabolic state of B cells might be the contributing factors to the dysfunctionality of autoimmune B cells. Understanding B-cell metabolism in autoimmunity is important as it can give rise to new treatments. Recent investigations have revealed that alterations in metabolism occur in the activation of B cells. Several reports have suggested that germinal center (GC) B cells of individuals with systemic lupus erythematosus (SLE) have altered metabolic function. GCs are unique microenvironments in which the delicate and complex process of B-cell affinity maturation occurs through somatic hypermutation (SHM) and class switching recombination (CSR) and where Bcl6 tightly regulates B-cell differentiation into memory B-cells or plasma cells. GC B cells rely heavily on glucose, fatty acids, and oxidative phosphorylation (OXPHOS) for their energy requirements. However, the complicated association between GC B cells and their metabolism is still not clearly understood. Here, we review several studies of B-cell metabolism, highlighting the significant transformations that occur in GC progression, and suggest possible approaches that may be investigated to more precisely target aberrant B-cell metabolism in SLE.

The Impact of Glycolysis and Its Inhibitors on the Immune Response to Inflammation and Autoimmunity

“…The upregulated glycolysis delivers a higher amount of pyruvate for oxidative phosphorylation. Further, other substrates, such as glutamine and fatty acids, are incorporated into OXPHOS [ 18 ].…”

“…However, the discovery of the upregulated glycolysis process in activated immune cells opened up new avenues for PET as a tool for inflammation diagnosis. As a result, Guidelines for 18 F-FDG Use in Inflammation and Infection were published for use in Europe and the United States [46]. It should be emphasized that more data than those currently available are needed in order to advance PET imaging as a first-line diagnostic tool.…”

“…It should be emphasized that more data than those currently available are needed in order to advance PET imaging as a first-line diagnostic tool. However, based on a cumulated reported accuracy analysis, 18 F-FDG PET could be applied for sarcoidosis [47], peripheral bone osteomyelitis [48], suspected spinal infections, and fever of unknown origin (FUO) diagnoses [49]. Moreover, an evaluation of metastatic infection of high-risk patients with bacteremia [50] and primary evaluation of vasculitides [51] could be performed.…”

Efficacy and safety of telitacicept in patients with lupus nephritis

“…B cells play a pivotal role in autoantibody generation, cytokine secretion and antigen presentation in SLE ( 6 ). Belimumab, a B cell-targeted therapy approved for patients with SLE aged ≥5 years ( 7 ), has been used for the treatment of LN in studies such as the international Belimumab in LN (Bliss-LN) trial.…”

The metabolic plasticity of B cells

“…At the molecular level, key regulators of activated B-cell functions exert a parallel control on metabolism. Therefore, alterations in B cells leading to diseases such as autoimmunity, immune deficiency and B-cell lymphomagenesis occur in the context of abnormal B-cell metabolism, as recently reviewed (Boothby and Rickert, 2017;Iperi et al, 2021;Raza and Clarke, 2021;Shiraz et al, 2022). Thus, understanding normal and dysfunctional B-cell metabolism may uncover potential avenues for interventions to harness pathogenic activities of B cells.…”