Class II MHC cytoplasmic domain-mediated signaling in B cells: A tail of two signals

Harton, Jonathan A.

doi:10.1016/j.humimm.2018.07.232

Cited by 7 publications

(9 citation statements)

References 62 publications

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“…Increasing evidence from cancer genomic and proteomic outline provide a novel research line where PKCs isoenzymes largely act as tumor suppressors and therefore their activity should be restored instead of inhibited in antitumor approaches (Newton 2018). However the clear immunologic role of PKC in lymphocytes biology is still to be portrayed and progresses in this area are still to come (Harton 2019).…”

Section: Pkcs Role In Bcr Signaling Eventsmentioning

confidence: 99%

Signal Transduction in Immune Cells and Protein Kinases

Neagu

Constantin

2021

Advances in Experimental Medicine and Biology

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Immune response relies upon several intracellular signaling events. Among the protein kinases involved in these pathways, members of the protein kinase C (PKC) family are prominent molecules because they have the capacity to acutely and reversibly modulate effector protein functions, controlling both spatial distribution and dynamic properties of the signals. Different PKC isoforms are involved in distinct signaling pathways, with selective functions in a cell-specific manner.In innate system, Toll-like receptor signaling is the main molecular event triggering effector functions. Various isoforms of PKC can be common to different TLRs, while some of them are specific for a certain type of TLR. Protein kinases involvement in innate immune cells are presented within the chapter emphasizing their coordination in many aspects of immune cell function and, as important players in immune regulation.In adaptive immunity T-cell receptor and B-cell receptor signaling are the main intracellular pathways involved in seminal immune specific cellular events. Activation through TCR and BCR can have common intracellular pathways while others can be specific for the type of receptor involved or for the specific function triggered. Various PKC isoforms involvement in TCR and BCR Intracellular signaling will be presented as positive and negative regulators of the immune response events triggered in adaptive immunity.

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Section: Pkcs Role In Bcr Signaling Eventsmentioning

confidence: 99%

Signal Transduction in Immune Cells and Protein Kinases

Neagu

Constantin

2021

Advances in Experimental Medicine and Biology

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“…Interestingly, similar outcomes and signaling pathways to MHC-I stimulation have been described after stimulation of MHC-II molecules in professional antigen-presenting cells, such as B cells and DCs [reviewed in (131)], as well as in other immune cells, like T cells and monocytes (132)(133)(134). In B cells, reverse MHC-II signaling was suggested to play a role in B cell activation, proliferation, differentiation or apoptosis after B cell-T cell interaction [reviewed in (135)(136)(137)], and also killing of malignant B cells (135,138). Similar to MHC-I, both cytoplasmic tail-dependent and -independent mechanisms have been proposed for reversed MHC-II signaling (135,136).…”

Section: ) (mentioning

confidence: 99%

“…In B cells, reverse MHC-II signaling was suggested to play a role in B cell activation, proliferation, differentiation or apoptosis after B cell-T cell interaction [reviewed in (135)(136)(137)], and also killing of malignant B cells (135,138). Similar to MHC-I, both cytoplasmic tail-dependent and -independent mechanisms have been proposed for reversed MHC-II signaling (135,136). Another similarity to reverse MHC-I signaling is the location of MHC-II signaling molecules in lipid rafts.…”

Section: ) (mentioning

confidence: 99%

Reverse Signaling by MHC-I Molecules in Immune and Non-Immune Cell Types

et al. 2020

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Major histocompatibility complex (MHC) molecules are well-known for their role in antigen (cross-) presentation, thereby functioning as key players in the communication between immune cells, for example dendritic cells (DCs) and T cells, or immune cells and their targets, such as T cells and virus-infected or tumor cells. However, much less appreciated is the fact that MHC molecules can also act as signaling receptors. In this process, here referred to as reverse MHC class I (MHC-I) signaling, ligation of MHC molecules can lead to signal-transduction and cell regulatory effects in the antigen presenting cell. In the case of MHC-I, reverse signaling can have several outcomes, including apoptosis, migration, induced or reduced proliferation and cytotoxicity towards target cells. Here, we provide an overview of studies showing the signaling pathways and cell outcomes upon MHC-I stimulation in various immune and non-immune cells. Signaling molecules like RAC-alpha serine/threonine-protein kinase (Akt1), extracellular signal-regulated kinases 1/2 (ERK1/2), and nuclear factor-κB (NF-κB) were common signaling molecules activated upon MHC-I ligation in multiple cell types. For endothelial and smooth muscle cells, the in vivo relevance of reverse MHC-I signaling has been established, namely in the context of adverse effects after tissue transplantation. For other cell types, the role of reverse MHC-I signaling is less clear, since aspects like the in vivo relevance, natural MHC-I ligands and the extended downstream pathways are not fully known.The existing evidence, however, suggests that reverse MHC-I signaling is involved in the regulation of the defense against bacterial and viral infections and against malignancies. Thereby, reverse MHC-I signaling is a potential target for therapies against viral and bacterial infections, cancer immunotherapies and management of organ transplantation outcomes.

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“…MHCII molecules can activate multiple distinct downstream signaling pathways (reviewed in Refs. [1][2][3]. The cytoplasmic domain of the MHCII ab heterodimer can directly activate an adenylate cyclase to drive cAMP production, which results in activation of protein kinase C (PKC) and B cell activation (4) (reviewed in Refs.…”

Section: Introductionmentioning

confidence: 99%

“…The cytoplasmic domain of the MHCII ab heterodimer can directly activate an adenylate cyclase to drive cAMP production, which results in activation of protein kinase C (PKC) and B cell activation (4) (reviewed in Refs. 1,2). In contrast, MHCII can activate an src/Syk-dependent signaling pathway, likely via an associated signaling molecule (see below), that results in a downstream intracellular calcium response (reviewed in Refs.…”

Section: Introductionmentioning

confidence: 99%

Signaling Cross-Talk between MHC Class II Molecular Conformers in Resting Murine B Cells

Drake

2019

ImmunoHorizons

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In addition to functioning as a ligand to engage TCRs and drive TCR signaling, MHC class II molecules are signaling molecules that generate a number of signals within APCs, such as B lymphocytes. Moreover, MHC class II signaling is critical for B cell activation and development of a robust humoral immune response. Murine class II molecules exist in two distinct conformational states, based primarily on the differential pairing of transmembrane domain GxxxG dimerization motifs (i.e., M1-and M2-paired class II). This laboratory has previously reported that the binding of a multimerized form of an anti-class II mAb that selectively recognizes M1-paired I-A k class II drives intracellular calcium signaling in resting murine B cells and that this signaling is dependent on both src and Syk protein tyrosine kinase activity. In contrast, multimerized forms of two different anti-I-A k mAbs that bind both M1-and M2-paired class II fail to elicit a response. In this report, a flow cytometry-based calcium flux assay is used to demonstrate that coligation of M1-and M2-paired I-A k class II results in the active and selective inhibition of M1-paired I-A k class II B cell calcium signaling by M2-paired class II molecules. Because M1-and M2-paired class II can be loaded with different sets of peptides derived from Ags acquired by distinct pathways of endocytosis, these findings suggest an MHC class II signaling-based mechanism by which CD4 T cells of differing specificities can either enhance or suppress B cell activation. ImmunoHorizons, 2019, 3: 28-36.

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Class II MHC cytoplasmic domain-mediated signaling in B cells: A tail of two signals

Cited by 7 publications

References 62 publications

Signal Transduction in Immune Cells and Protein Kinases

Signal Transduction in Immune Cells and Protein Kinases

Reverse Signaling by MHC-I Molecules in Immune and Non-Immune Cell Types

Signaling Cross-Talk between MHC Class II Molecular Conformers in Resting Murine B Cells

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