BAFF Augments Certain Th1-Associated Inflammatory Responses

Abstract

B cell-activating factor belonging to the TNF family (BAFF; BLyS) is a critical regulator of B cell maturation and survival, and its overexpression in BAFF transgenic (Tg) mice results in the development of autoimmune disorders. BAFF also affects T cell function through binding to one of the BAFF receptors, BAFF-R. Using BAFF Tg mice, we examined a typical Th1-mediated response, the cutaneous delayed-type hypersensitivity reaction, and found a much greater degree of paw swelling and inflammation than in control mice. Importantly, delayed-type hypersensitivity scores correlated directly with BAFF levels in serum. Conversely, in a Th2-mediated model of allergic airway inflammation, BAFF Tg mice were largely protected and showed markedly reduced Ag-specific T cell proliferation and eosinophil infiltration associated with the airways. Thus, local and/or systemically distributed BAFF affects Th1 and Th2 responses and impacts on the course of some T cell-mediated inflammatory reactions. Our results are consistent with the idea that BAFF augments T cell as well as B cell responses, particularly Th1-type responses. Results in BAFF Tg mice may reflect the situation in certain autoimmune patients or virally infected individuals, because BAFF levels in blood are comparable.

The effects of BAFF and BAFF-R-Fc fusion protein in immune thrombocytopenia

“…9,10 In addition, we also found rhBAFF could increase the production of IFN-␥ but had no obvious effect on the secretion of IL-4 in in vitro experiments, consistent with earlier studies showing typical Th1-mediated responses and reduced Th2-mediated responses in BAFF transgenic mice. 16 ITP is a heterogeneous disease; besides humoral immune abnormalities, several T-cell abnormalities have been demonstrated in patients with ITP, including Th1 bias, the inhibition of autologous megakaryocyte apoptosis by CD8 ϩ T cells, and cell-mediated cytotoxic lysis of platelets by CTLs. 3,4,[8][9][10]35 Our results indicated that elevated BAFF not only was involved in humoral immune abnormalities by promoting the survival of B cells, but also may be involved in the cellular immunity abnormalities by promoting the survival of T cells.…”

“…[13][14][15] In addition, BAFF also augments certain Th1-associated inflammatory responses. 16 BAFF binds to 3 receptors: B-cell maturation antigen (tumor necrosis factor receptor superfamily, member 17 [TNFRSF17]), transmembrane activator and calcium-modulating cyclophilin ligand (CAML) interactor (TACI; TNFRSF13B), and BAFF receptor (BR3/BAFF-R; TNFRSF13C). 17,18 BR3, identified as the crucial receptor for B-cell survival, is expressed on a wide range of B-cell subsets, including immature, transitional, mature, memory, and germinal center B cells, as well as on plasma cells.…”

B cell activating factor (BAFF) in the natural history of chronic hepatitis C virus liver disease and mixed cryoglobulinaemia

“…Over-expression of BAFF in mice and in humans is associated with autoimmune disorders such as Sjögren's syndrome (SS) and systemic lupus erythematosus (SLE) [4].…”

Increased CD4+Foxp3+ T Cells in BAFF-Transgenic Mice Suppress T Cell Effector Responses

“…A potential role for BAFF in regulating T cell activation and function is also supported by in vivo studies. BAFF-transgenic (Tg) mice exhibit exaggerated T-dependent Ag responses, enhanced delayed-type hypersensitivity (DTH) responses, and have an expanded CD4 ϩ CD62L low , CD44 high memory population (9). Conversely, loss of BAFF signaling impairs the development of Ag-specific T cell responses (6).…”