PILLARS OF IMMUNOLOGY
Long Live the Plasma Cell: The Basis of Sustained Humoral Immunity
This Pillars of Immunology article is a commentary on “Humoral immunity due to long-lived plasma cells,” a pivotal article written by M. K. Slifka, R. Antia, J. K. Whitmire, and R. Ahmed, and published in Immunity, in 1998. https://pubmed.ncbi.nlm.nih.gov/9529153/. The Journal of Immunology, 2022, 209: 3–4.
ANTIGEN RECOGNITION AND RESPONSES
The Pre-Existing Human Antibody Repertoire to Computationally Optimized Influenza H1 Hemagglutinin Vaccines
Seasonally vaccinated subjects possess functional Abs to H1 COBRA HAs.
H1 COBRA HA-reactive B cell responses were similar across vaccine seasons.
At Critically Low Antigen Densities, IgM Hexamers Outcompete Both IgM Pentamers and IgG1 for Human Complement Deposition and Complement-Dependent Cytotoxicity
Complement is activated more potently by hexameric IgM versus pentameric IgM or IgG1.
These differences in activity are observed at low, but not high, Ag densities.
Mouse Liver B Cells Phagocytose Streptococcus pneumoniae and Initiate Immune Responses against Their Antigens
Phagocytic B cells induced anti-PspA IgG production in the hosts.
Phagocytic B cells presented bacterial peptides to spleen CD4+ T cells.
Phagocytic B cells were not involved in affinity maturation.
Profibrotic Role of Inducible Heat Shock Protein 90α Isoform in Systemic Sclerosis
Fibroblasts from fibrotic mouse skin overexpress Hsp90α mRNA.
Hsp90α-deficient fibrotic mice exhibit reduced skin thickness compared with wild-type mice.
Higher serum levels of Hsp90α are associated with dSSc and pulmonary fibrosis.
CLINICAL AND HUMAN IMMUNOLOGY
Therapeutic Effect of Anti-CD52 Monoclonal Antibody in Multiple Sclerosis and Its Animal Models Is Mediated via T Regulatory Cells
Anti-CD52 mAb suppresses EAE via Treg expansion.
IL-7 induces expansion of CD4+CD25+CD127− Tregs from RRMS patients.
Anti-CD52 mAb induces suppression of IL-17+ and IFN-γ+ CD4+ cell responses.
STAP-2 Is a Novel Positive Regulator of TCR-Proximal Signals
STAP-2 enhances TCR signaling via the binding to CD3ζ ITAM and LCK.
STAP-2-deficient mice show an impaired induction of autoimmune diseases.
STAP-2-overexpressing transgenic mice show severe phenotypes of autoimmune diseases.
High-Fat Diet–Induced Obesity Alters Dendritic Cell Homeostasis by Enhancing Mitochondrial Fatty Acid Oxidation
Obesity blunts the Ag-presenting capacity of mouse splenic DCs.
These dysfunctional DCs show major transcriptomic and mitochondrial alterations.
Enhanced mitochondrial fatty acid oxidation drives DC dysfunction in obesity.
IMMUNE SYSTEM DEVELOPMENT
Realization of the T Lineage Program Involves GATA-3 Induction of Bcl11b and Repression of Cdkn2b Expression
GATA3 is required for a Notch-induced program of T lineage differentiation.
GATA3 is required for Bcl11b expression, and together they repress the Cdkn2 locus.
Dysregulated Cdkn2 expression leads to apoptosis of early T lineage cells.
Monogenic TCRβ Assembly and Expression Are Paramount for Uniform Antigen Receptor Specificity of Individual αβ T Lymphocytes
TCR protein pairing restrictions can shape the αβ TCR repertoire.
These restrictions have a negligible role for uniform specificity of αβ T cells.
Monogenic TCRβ assembly is fundamental for uniform specificity of αβ T cells.
IMMUNOTHERAPY AND VACCINES
Viral Delivery of IL-7 Is a Potent Immunotherapy Stimulating Innate and Adaptive Immunity and Confers Survival in Sepsis Models
MVA-vectorized IL-7 stimulates cells from the innate and adaptive lineage.
It confers protection in sepsis mice.
Its mechanism of action is broader than a nonvectorized IL-7 formulation.
Improved Durability to SARS-CoV-2 Vaccine Immunity following Coimmunization with Molecular Adjuvant Adenosine Deaminase-1
ADA-1 enhances humoral responses by inducing durable, high-affinity, and neutralizing Abs.
ADA-1 enhances cellular responses by inducing durable Ag-specific T and B cells.
ADA-1–enhanced humoral and cellular responses translated to increased protection.
INFECTIOUS DISEASE AND HOST RESPONSE
Type I IFN Signaling Is Essential for Preventing IFN-γ Hyperproduction and Subsequent Deterioration of Antibacterial Immunity during Postinfluenza Pneumococcal Infection
IFN-γ plays a dominant role in the deterioration of IAV/bacterial coinfection.
IFN-γ induces alveolar macrophage depletion during IAV/bacterial coinfection.
IFN-α/β signaling prevents IFN-γ hyperproduction during IAV/bacterial coinfection.
INNATE IMMUNITY AND INFLAMMATION
Extracellular pH Controls Chemotaxis of Neutrophil Granulocytes by Regulating Leukotriene B4 Production and Cdc42 Signaling
Neutrophil chemotaxis towards C5a depends on intracellular and extracellular pH.
pH controls LTB4 secretion and Cdc42 activation.
Chemotaxis requires the activity of the Na+/H+ exchanger NHE1.
MOLECULAR AND STRUCTURAL IMMUNOLOGY
Efficient Identification of Tembusu Virus CTL Epitopes in Inbred HBW/B4 Ducks Using a Novel MHC Class I–Restricted Epitope Screening Scheme
A new scheme to identify CTL epitopes of unknown MHC-I based on RPLD-MS technology is described.
The crystal structure of Anpl-UAA*76 is detailed.
The conserved Anpl-UAA*76–restricted TMUV CTL epitopes are discussed.
Spinal Cord Injury Impairs Lung Immunity in Mice
SCI impairs leukocyte recruitment and transcriptional control of lung immunity.
Impaired lung immunity after SCI creates a microenvironment permissive for infection.
Boosting leukocyte recruitment to the lung does not reduce bacterial burden after SCI.
Identification of RPL15 60S Ribosomal Protein as a Novel Topotecan Target Protein That Correlates with DAMP Secretion and Antitumor Immune Activation
RPL15 is identified as a novel TPT target.
TPT induces DAMP secretion from cancer cells via its binding to RPL15.
RPL15 inhibition sensitizes B16-F10 tumors against PD-1 blockade.
Apo-Form Selective Inhibition of IDO for Tumor Immunotherapy
A novel apo-IDO1 inhibitor with potent in vitro and in vivo activity was developed.
The cocrystal of B37 and IDO1 complex helps elucidate its inhibition mechanism.
The combination of B37 and anti-PD1 Ab synergistically inhibited tumor growth.
On the cover: Structural depiction of Ab Fab fragments in complex with the 2009 pandemic influenza HA protein (blue). Two head domain-binding Fabs, 5J8 (orange) and Ab6649 (beige), and one stem domain-binding Fab, CR6261 (green), are shown. The newly discovered anchor Ab, P1-05, is modeled in yellow. Nagashima, K., J. V. Dzimianski, J. Han, N. Abbadi, A. D. Gingerich, F. Royer, S. O'Rourke, G. A. Sautto, T. M. Ross, A. B. Ward, R. M. DuBois, and J. J. Mousa. 2022. The pre-existing human antibody repertoire to computationally optimized influenza H1 hemagglutinin vaccines. J. Immunol. 209: 5-15.
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