The BAFF/APRIL system: Emerging functions beyond B cell biology and autoimmunity

Abstract

The BAFF system plays a key role in the development of autoimmunity, especially in systemic lupus erythematosus (SLE). This often leads to the assumption that BAFF is mostly a B cell factor with a specific role in autoimmunity. Focus on BAFF and autoimmunity, driven by pharmaceutical successes with the recent approval of a novel targeted therapy Belimumab, has relegated other potential roles of BAFF to the background. Far from being SLE-specific, the BAFF system has a much broader relevance in infection, cancer and allergy. In this review, we provide the latest views on additional roles of the BAFF system in health and diseases, as well as an update on BAFF and autoimmunity, with particular focus on current clinical trials.

Aiolos Overexpression in Systemic Lupus Erythematosus B Cell Subtypes and BAFF-Induced Memory B Cell Differentiation Are Reduced by CC-220 Modulation of Cereblon Activity

“…We show in this study that the soluble factors BAFF, IL-2, and IL-21 implicated in SLE pathogenesis (32,37,38,76,(96)(97)(98) have the capacity to contribute to disease by inducing B cell proliferation, plasmablast differentiation, and Ab secretion from a select memory pool of B cells consisting of CD27 + memory and CD27 2 IgD 2 DN memory-like B cell subtypes. Naive B cells, in contrast, are incapable of responding to BAFF, IL-2, and IL-21 in the absence of CD40L, a signal most commonly provided by T cell contact in the germinal center within secondary lymphoid structures.…”

“…BAFF is produced as type II transmembrane protein and cleaved into its soluble form at a furin protease site and released in a soluble form (36). BAFF binds to three different receptors: BAFF receptor (BAFF-R), transmembrane activator and Ca 2+ modulator and cyclophilin ligand interactor (TACI), and B cell maturation Ag (BCMA), the functions of which are reviewed elsewhere (37,38). Although BAFF may remain in an active membrane-bound form, soluble BAFF is required for B cell homeostasis and enhances the survival of plasmablasts (39,40).…”

Re-thinking the functions of IgA+plasma cells

“…However, caution must be exercised as Atacicept worsened Multiple Sclerosis symptoms (an unexpected result given the efficacy of B cell depletion by Rituximab in the same disease setting). 56,57 In addition to the BM, the gut LP is a rich source of PC, particularly IgA C PC. Specifically, B cells primed in the PP egress through the efferent lymphatics, and following recirculation through the thoracic duct, home to the small intestinal LP due to their expression of the a4b7 homing receptor as well as the CCR9 and CCR10 chemokine receptors.…”

Systems vaccinology: Probing humanity’s diverse immune systems with vaccines

“…In the case of neutralizing antibody responses, a different gene signature was found to be predictive. One of the genes within this signature was TNFRSF17, which encodes the receptor for the B-cell growth factor BLyS-BAFF, which is known to play a key role in the differentiation of plasma cells (35).…”