Immunology & Cell Biology’s Top 10 original research articles 2019–2020
When the year draws to a close, it is often symbolized by an old man who passes the mantle on to a newborn for the next year. With the passing of this mantle, we have completed another year of fantastic research, and it is time to celebrate the Top 10 original research articles for 2019–2020. These articles were chosen by the Immunology & Cell Biology (ICB) Editorial Team on 1 July 2020, from the manuscripts accepted in the previous 12 months and have been compiled here in our first Virtual Issue for 2021. Showcasing the high quality and breadth of immunological research published in ICB, these articles are revealed below in chronological order.
ICB’s Top 10 from 1 July 2019 to 30 June 2020 (in chronological order of publication)
- Robinson et al.1 BAFF, IL-4 and IL-21 separably program germinal centre-like phenotype acquisition, BCL6 expression, proliferation and survival of CD40L-activated B cells in vitro
- Jeong et al.2 Over-expression of p190RhoGEF enhances B-cell activation and germinal center formation in T-cell-dependent humoral immune responses
- Watson et al.3 A comparison of immunoglobulin IGHV, IGHD and IGHJ genes in wild-derived and classical inbred mouse strains
- Sood et al.4 Differential interferon-gamma production potential among naïve CD4+ T cells exists prior to antigen encounter
- Chung et al.5 Systems Immunology reveals a linked IgG3–C4 response in patients with acute rheumatic fever
- Patton et al.6 Daptomycin-resistant Staphylococcus aureus clinical isolates are poorly sensed by dendritic cells
- van der Heiden et al.7 Characterization of the γδ T-cell compartment during infancy reveals clear differences between the early neonatal period and 2 years of age
- Obeidy et al.8 Partial loss of actin nucleator actin-related protein 2/3 activity triggers blebbing in primary T lymphocytes
- Li et al.9 Host CD8α+ and CD103+ dendritic cells prime transplant antigen-specific CD8+ T cells via cross-dressing
- Ge et al.10 Neutrophils play an ongoing role in preventing bacterial pneumonia by blocking the dissemination of Staphylococcus aureus from the upper to the lower airways
Our criteria for selection are simple: novelty, impact, clarity and scientific excellence. Together, these original research articles cover a wide range of topics including the cellular mechanics of T-cell movement, the factors controlling germinal center-like B-cell characteristics, the linkage of M protein-specific immunoglobulin (Ig)G3 and C4 to acute rheumatic fever and the role of neutrophils in controlling the localization of Staphylococcus aureus infection in the respiratory tract.
Taking a peek at our Top 10
Like the new year coming in as a babe, we begin with a study by van der Heiden et al.7 that investigates the γδ T-cell compartment from birth to adulthood. This work reports that by 2 years of age the functionality of the γδ T-cell compartment is comparable to that of adults while γδ T cells from extremely preterm neonates display clear phenotypic and functional differences from their full-term counterparts.7 This study sheds light on the early events shaping immune competency and protection against infectious diseases in newborns.
Moving from newborns to naïve T cells, Sood et al.4 ask the question, “Are all naïve T cells equal?” While it is clear that extrinsic factors during the initial activation of naïve T cells shape their responses, this study investigated whether each naïve T cell already has a predetermined, intrinsic capacity to respond. Using OTII mice to remove variation due to different T-cell receptors, the investigators observed that CD5lowCD4+ T cells had a greater potential to produce interferon-γ than CD5highCD4+ T cells.4 Because CD5 is a negative regulator of T-cell receptor signaling, this work reveals the central role of T-cell receptor signal strength in T-helper-cell subset differentiation in vitro and in vivo in a manner that is independent of cognate antigen.
The articles by Li et al.9 and Obeidy et al.8 also center on T-cell function, but this time on two factors that enable cytotoxic T-cell (CTL) effector function: dendritic cell (DC) subsets and actin-related protein 2/3 (Arp2/3). Looking at how CTLs are primed to recognize allografts, Li et al.9 report that not only are the CD8α+ and CD103+ DCs the key antigen-presenting cells driving alloreactive recognition, but also these DC subsets pick up and present alloantigens in a process known as “cross-dressing” (i.e. the transfer of preformed major histocompatibility complex–peptide complexes). In contrast to antigen presentation, Obeidy et al 8 look within the CTL at its actin cytoskeleton to understand how Arp2/3, which is an essential regulator of actin networks, is involved in optimal CTL function. They find that without Arp2/3 maintaining the mechanophysical membrane integrity, CTL locomotion and cytotoxicity are impaired.8 These two studies underscore the importance of cellular networks in CTL activities.
While CD40 has arisen as a crucial activator of B cells in T-cell-dependent humoral immune responses, studies by Jeong et al.2 and Robinson et al.1 explore the other signals involved in germinal center formation and phenotypic acquisition. Looking at the signaling pathways downstream of CD40, Jeong et al.2 identify that p190RhoGEF augments plasma cell generation and germinal center formation in vivo. Robinson and colleagues further dissect the events directing germinal center B cells in an in vitro model and find that interleukin-4, BAFF and interleukin-21 have unique and complementary roles in coordinating proliferation, survival and phenotype, which shape the fate of germinal center B cells.1
Talking about B cells leads us naturally to antibodies and antibody diversity, the topic of the article by Watson et al.3 By comparing the diversity of the IgH gene loci of wild-derived and inbred strains of mice, the investigators find an unexpected level of genetic variation and propose that these loci may represent a mosaic of genes derived from a variety of different origins.3 These findings suggest that the current system of nomenclature, which relies on positional information from one inbred strain, may not be transferrable to other genetically distinct strains.3
Our final three articles focus on detrimental and protective immune responses to the bacterial pathogens, Group A streptococcus and Staphylococcus aureus.5, 6, 10 Chung et al.5 use a systems immunology approach to uncover a possible role for anti-M protein-specific IgG3 and C4 in acute rheumatic fever, which can lead to permanent heart damage and rheumatic heart disease. Acute rheumatic fever is believed to be driven by the development of autoreactive antibodies through molecular mimicry, and thus, this proposed linkage has important implications in biomarker development as well as providing critical insight into the pathogenesis of acute rheumatic fever.5 The study by Patton et al.6 looks in more detail at how the characteristics of the bacteria may influence the ability of the immune response (and DC, in particular) to detect them. They find that strains of S. aureus that develop resistance to daptomycin invoke a reduced DC response compared with their daptomycin-sensitive counterparts.6 The investigators further identify point mutations in two bacterial genes (cls2 and mprF) that impact the ability of DC to sense these strains.6 Finally, our last article by Ge et al.10 dissects the role of neutrophils in controlling S. aureus lung infections. By depleting neutrophils in vivo, the authors show that neutrophils are key to restricting S. aureus to the upper airways. Furthermore, boosting neutrophil numbers with granulocyte-colony stimulating-factor in a model of influenza A virus-mediated S. aureus pneumonia led to reduced disease severity and prevented bacterial dissemination.10
Altogether, this Virtual Issue showcases the outstanding contributions of our authors to the fields of immunology and cell biology. Finally, I would like to thank the authors of these 10 articles as well as the many excellent contributors who have published their exciting research in Immunology & Cell Biology.
