Aminoacyl tRNA Synthetase–Interacting Multifunctional Protein 1 Acts as a Novel B Cell–Activating Factor In Vitro and In Vivo

Abstract

Endogenous B cell–activating factors play pivotal roles in defense mechanisms by regulating B cell responses. We previously reported that aminoacyl tRNA synthetase–interacting multifunctional protein 1 (AIMP1) functions as a novel proinflammatory cytokine that activates macrophages and dendritic cells. However, roles of AIMP1 in B cell responses have not been studied. In this study, we investigated the effects of AIMP1 on B cell responses and their underlying mechanisms. AIMP1 induced the expression of surface activation markers on murine B cells and the proliferation of B cells. Additionally, AIMP1 increased the expression of activation-induced deaminase and class switch recombination in B cells. AIMP1 also had synergistic effects on B cell activation when combined with CD40 stimulus. Intracellular signaling experiments showed that AIMP1 activated B cells through a protein kinase C/NF-κB signaling pathway. Importantly, i.v. injection of AIMP1 into mice increased the expression of CD69 on splenic B cells and significantly enhanced Ag-specific Ab production. Taken together, our results show that AIMP1 acts as a novel B cell–activating factor. AIMP1-mediated B cell activation and the involvement of AIMP1 in diseases will provide additional information for therapeutic strategies.

Aminoacyl-tRNA synthetases, therapeutic targets for infectious diseases

“…Extracellularly, AIMP1 activates innate immune cells such as macrophages and monocytes to produce inflammatory cytokines through MAPK signaling [43] and induces maturation of BMDCs [44]. AIMP1 potentiates the link between innate and adaptive immunity by activating NK cells [45] and B cells [46] and by promoting IL-12-mediated T-helper type 1 (T H 1) cell immunity [47]. AIMP1 expression in BMDCs directly promoted T H 1 cell polarization, which is characterized by the secretion of IL-12 and IFN-γ from antigenpresenting cells and T cells, respectively, and is associated with the generation of cell-mediated adaptive immune responses [48].…”

“…AIMP1 is also secreted as a full-length form or as a 22 kDa Cterminal EMAPII domain [99]. Secreted AIMP1 displayed diverse biological functions, including upregulation of proinflammatory genes [43] and activation of immune cells [46,100]. The EMAPII domain activated host immune responses by acting as a proinflammatory cytokine or as a chemoattractant to induce endothelial/mononuclear cell migration [99,101,102].…”

MHC class I and II peptide homology regulates the cellular immune response

“…Earlier studies demonstrated that genetic ablation of AIMp1 significantly enhanced T H 2‐polarized airway hyperreactivity in a model of allergic inflammation, 44 while in vitro studies showed that recombinant AIMp1 protein induced upregulated IL‐12 secretion from bone marrow‐derived DC and enhanced the generation of IFN‐γ‐secreting CD4 + T‐cells 43,45 . Recombinant AIMp1 also induced B‐cell activation, proliferation, and class switch recombination toward the T H 1‐specific IgG 2 isotype with increased antigen‐specific antibody production 46 . More recent work demonstrated that dendritic cell ‐expressed AIMp1 is a critical component of the T H 1 regulatory cascade and absolutely required for IL‐12 production, downstream T H 1 polarization, and functional antiviral and antitumor immunity in C57BL/6 and 129Sv mice 29 …”

Lysyl–Transfer RNA Synthetase Induces the Maturation of Dendritic Cells through MAPK and NF-κB Pathways, Strongly Contributing to Enhanced Th1 Cell Responses

“…We previously demonstrated that aaRS-interacting multifunctional protein 1 (AIMP1), an aaRS-associated factor, stimulated the activation of immune cells, including DCs, B cells, and NK cells (7,15,16). As AIMP1 and KRS are capable of activating macrophages and are closely associated within the multisynthetase complex (17,18), we, therefore, questioned whether KRS affects the phenotypes and functions of DCs.…”