Ly6C expression differentiates plasma cells from other B cell subsets in mice

Wrammert, Jens; Källberg, Eva; Agace, William W.; Leanderson, Tomas

doi:10.1002/1521-4141(200201)32:1<97::aid-immu97>3.0.co;2-y

Cited by 45 publications

(40 citation statements)

References 27 publications

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“…Upon closer examination, we discovered that the previous study had used an anti-Gr-1 antibody (clone RB6-8C5) to deplete granulocytes (31). Gr-1 is a shared epitope present on the Ly6C and Ly6G molecules (49), so administration of this antibody would deplete multiple populations of cells expressing Ly6C, including monocytes and macrophages (50), bone marrow cells (51), thymocytes (52), B cells (53), and subsets of T CD8ϩ (54) and T CD4ϩ (52). Our study targeted Ly6G specifically using a different antibody (clone 1A8) that does not recognize significant populations of activated T or B lymphocytes (55).…”

Section: Discussionmentioning

confidence: 99%

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection

Kaminsky

Sei

Parekh

et al. 2015

J Virol

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Viruses that spread systemically from a peripheral site of infection cause morbidity and mortality in the human population. Innate myeloid cells, including monocytes, macrophages, monocyte-derived dendritic cells (mo-DC), and dendritic cells (DC), respond early during viral infection to control viral replication, reducing virus spread from the peripheral site. Ectromelia virus (ECTV), an orthopoxvirus that naturally infects the mouse, spreads systemically from the peripheral site of infection and results in death of susceptible mice. While phagocytic cells have a requisite role in the response to ECTV, the requirement for individual myeloid cell populations during acute immune responses to peripheral viral infection is unclear. In this study, a variety of myeloid-specific depletion methods were used to dissect the roles of individual myeloid cell subsets in the survival of ECTV infection. We showed that DC are the primary producers of type I interferons (T1-IFN), requisite cytokines for survival, following ECTV infection. DC, but not macrophages, monocytes, or granulocytes, were required for control of the virus and survival of mice following ECTV infection. Depletion of either plasmacytoid DC (pDC) alone or the lymphoid-resident DC subset (CD8␣ ؉ DC) alone did not confer lethal susceptibility to ECTV. However, the function of at least one of the pDC or CD8␣ ؉ DC subsets is required for survival of ECTV infection, as mice depleted of both populations were susceptible to ECTV challenge. The presence of at least one of these DC subsets is sufficient for cytokine production that reduces ECTV replication and virus spread, facilitating survival following infection. IMPORTANCEPrior to the eradication of variola virus, the orthopoxvirus that causes smallpox, one-third of infected people succumbed to the disease. Following successful eradication of smallpox, vaccination rates with the smallpox vaccine have significantly dropped. There is now an increasing incidence of zoonotic orthopoxvirus infections for which there are no effective treatments. Moreover, the safety of the smallpox vaccine is of great concern, as complications may arise, resulting in morbidity. Like many viruses that cause significant human diseases, orthopoxviruses spread from a peripheral site of infection to become systemic. This study elucidates the early requirement for innate immune cells in controlling a peripheral infection with ECTV, the causative agent of mousepox. We report that there is redundancy in the function of two innate immune cell subsets in controlling virus spread early during infection. The viral control mediated by these cell subsets presents a potential target for therapies and rational vaccine design. P rior to the induction of the adaptive immune response, cells of the innate immune system are deployed early during viral infection to control the pathogen and limit its spread from the site of infection. Effector cells of the innate immune system include myeloid cell subsets: granulocytes (neutrophils, eosinophils, and b...

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Section: Discussionmentioning

confidence: 99%

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection

Kaminsky

Sei

Parekh

et al. 2015

J Virol

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“…In the B cell lineage, Ly6C expression is elevated in PCs. Although extensive characterization was not done, the highest expression was documented for IgA-secreting PCs (30). We therefore assessed the expression of Ly6C in the various mice.…”

Section: Tsc1 Deletion Promotes Pc Differentiationmentioning

confidence: 99%

mTOR Activation Promotes Plasma Cell Differentiation and Bypasses XBP-1 for Immunoglobulin Secretion

Benhamron

Pattanayak

Berger³

et al. 2015

Molecular and Cellular Biology

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T he endoplasmic reticulum (ER) is the port of entry into the secretory pathway. ER stress is a state of imbalance between the protein-folding capacities and the amount of proteins in the ER. A network of signaling pathways termed the unfolded protein response (UPR) restores the disrupted balance in the ER or executes apoptosis when ER stress becomes terminal. In mammalian cells, the UPR operates in three parallel pathways named for ER stress sensors: inositol-requiring enzyme 1 (IRE1), protein kinaselike endoplasmic reticulum kinase (PERK), and activating transcription factor 6 (ATF6). These sensors activate downstream signals that regulate gene transcription and protein synthesis (1).Following a signal to differentiate into plasma cells (PCs), the ER of a B cell expands and becomes permissive for the synthesis, proper folding, assembly, and secretion of copious amounts of antibodies. For reasons that are not fully understood, the remodeling of the ER in the course of PC differentiation is controlled solely by the IRE1/X-box binding protein 1 (XBP-1) pathway of the UPR (2, 3). In the absence of XBP-1 or IRE1, B cells develop normally to the mature state but yield long-lived PCs that secrete small amounts of Igs (4-7).Mammalian target of rapamycin (mTOR) is a key metabolic serine/threonine kinase which exists in at least two multisubunit complexes, referred to as mTOR complex 1 (mTORC1) and mTORC2 (8). mTORC1 funnels multiple signaling pathways from inside and outside the cell. When activated, mTORC1 promotes anabolic processes and enhances protein synthesis and cell growth (9). When it is inhibited, macroautophagy is induced (10). mTOR, primarily in the form of mTORC1, plays major roles in cancer and immune functions (11,12). Much of the knowledge on the role of mTOR in immune regulation has been obtained from loss-of-function experiments using rapamycin or analogs thereof. However, the effect that mTOR activation has on the immune system remains unclear. At the mature state of B cell development, mTOR is activated in response to Toll-like receptor and B cell receptor (BCR) stimulation downstream from the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Akt activates mTORC1 indirectly by reversing the tuber sclerosis complex (TSC) inhibition of mTOR. TSC is a complex that contains TSC1 and TSC2. Among many other functions, the mTOR pathway adjusts protein synthesis to the prosperity conditions of the cell. mTOR is activated when the ATP/AMP ratio or the intracellular pool of amino acids is high. The control of protein synthesis is regulated by mTOR-specific phosphorylation of 4E-BP1 and p70S6K1, both of which, when phosphorylated, mediate acceleration of protein synthesis and cell growth (13-15). Hence, inhibition of the mTOR globally reduces protein synthesis and cell size.We previously reported that mTOR is the predominant mechanism that controls protein synthesis in the late phase of lipopolysaccharide (LPS)-activated B cells, in a manner rigorously controlled by ER stress. Genetic ablation of TSC...

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“…Splenic and LP PC express Ly6C and its cross-linking positively regulates Ig production. 110 In addition, Ly6C supports homing of central memory CD8…”

Section: Ly6gmentioning

confidence: 99%

Re-thinking the functions of IgA⁺plasma cells

Gommerman

Rojas

Fritz³

2014

Gut Microbes

106

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Ly6C expression differentiates plasma cells from other B cell subsets in mice

Cited by 45 publications

References 27 publications

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection

mTOR Activation Promotes Plasma Cell Differentiation and Bypasses XBP-1 for Immunoglobulin Secretion

Re-thinking the functions of IgA⁺plasma cells

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Ly6C expression differentiates plasma cells from other B cell subsets in mice

Cited by 45 publications

References 27 publications

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection

Redundant Function of Plasmacytoid and Conventional Dendritic Cells Is Required To Survive a Natural Virus Infection

mTOR Activation Promotes Plasma Cell Differentiation and Bypasses XBP-1 for Immunoglobulin Secretion

Re-thinking the functions of IgA+plasma cells

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Re-thinking the functions of IgA⁺plasma cells