https://orcid.org/0000-0002-8941-4992
Peer Review History
| Original SubmissionJuly 20, 2020 |
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Dear Dr. Siebenlist, Thank you very much for submitting your manuscript "The NF-κB regulator Bcl-3 restricts terminal differentiation and promotes memory cell formation of CD8+ T cell in viral infection" for consideration at PLOS Pathogens. As with all papers reviewed by the journal, your manuscript was reviewed by members of the editorial board and bytwo independent reviewers. In light of the reviews (below this email), we would like to invite the resubmission of a significantly-revised version that takes into account the reviewers' comments. We specifically request you to provide data for the following comments. a) Show whether Bcl3 is expressed on different CD8 T cell subsets during LCMV infection b) Demonstrate if there is differential proliferation and or apoptosis of Wt and Bcl3-/- CD8 T cells c) (Optional) show the expression of perforin, gran B, Tbet, Eomes and other effector molecules of CD8 T cells in wt and Bsl3-/- mice. d) Provide control gates for Fig2 C/D FACS plots In addition, we request authors to provide explanation for the other comments raised by the reviewers. We cannot make any decision about publication until we have seen the revised manuscript and your response to the reviewers' comments. Your revised manuscript is also likely to be sent to reviewers for further evaluation. When you are ready to resubmit, please upload the following: [1] A letter containing a detailed list of your responses to the review comments and a description of the changes you have made in the manuscript. Please note while forming your response, if your article is accepted, you may have the opportunity to make the peer review history publicly available. The record will include editor decision letters (with reviews) and your responses to reviewer comments. If eligible, we will contact you to opt in or out. [2] Two versions of the revised manuscript: one with either highlights or tracked changes denoting where the text has been changed; the other a clean version (uploaded as the manuscript file). Important additional instructions are given below your reviewer comments. Please prepare and submit your revised manuscript within 60 days. If you anticipate any delay, please let us know the expected resubmission date by replying to this email. Please note that revised manuscripts received after the 60-day due date may require evaluation and peer review similar to newly submitted manuscripts. Thank you again for your submission. We hope that our editorial process has been constructive so far, and we welcome your feedback at any time. Please don't hesitate to contact us if you have any questions or comments. Sincerely, Rudra Channappanavar, DVM, Ph.D. Guest Editor PLOS Pathogens Volker Thiel Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************** Reviewer's Responses to Questions Part I - Summary Reviewer #1: In this manuscript, authors have characterized the role of Bcl-3 in terminal differentiation of memory CD8+ T cells. Using acute LCMV model, investigators show that BCL3 is critical for maintaining balance of terminal effector/memory cell balance during CD8+ T cell differentiation. This study lacks mechanistic details for observed differences in SLECs and MPECs post LCMV infection and recall responses. Thus, descriptive phenotypic changes in Knock-out mice in the absence of mechanistic details diminishes the importance of these findings. Nevertheless, overall findings are interesting and various conclusions are well supported by data generated using WT/Bcl-3 KO bone-marrow chimera and CD8-specific conditional Bcl-3 knock-out mice. Reviewer #2: This study is very interesting as it show the role of Bcl3 in generation of cd8 memory t cells. The study is well designed and uses various high end techniques and tools to make a conclusion. ********** Part II – Major Issues: Key Experiments Required for Acceptance Reviewer #1: 1. Authors show transient expression of Bcl-3 in CD8+ T cells post CD3/CD28 stimulation. Although this data indicates the transient induction of Bcl-3 post TCR stimulation, similar expression kinetics data for Bcl-3 in naïve, effector/memory CD8+ T cells post LCMV infection is critical as a premise to study the role of Bcl-3 in in vivo differentiation of CD8+ T cells post LCMV infection. 2. Mixed bone-marrow chimera experiments do not show overall differences in LCMV-specific CD8+ T cell responses after acute infection. Further, mixed chimera experiments do not rule out the role for Bcl-3 in other myeloid cells particularly APCs in regulation of effector versus memory T cell differentiation. Although authors have used conditional knock-out mice for CD8+ T cells to demonstrate cell-intrinsic role of Bcl-3 in efficient formation of memory CD8+ T cells, the choice of cre-strain indicate that there could be developmental defects in CD8+ T cells this conditional knock-out mice. 3. There is no clear mechanistic explanation for increased terminal effector cells over MPECs in Bcl-3-/- mice studies. Is this because of increased proliferation or increased survival/reduced apoptosis? Also, mixed bone marrow-chimera experiment show differential reconstitution of CD4/CD8 T cells in WT and KO cells. This data points initial differences in WT and KO cells could drive differential CD8+ T cell responses post LCMV challenge. 4. Data represents multiple experiments. Did authors pool data from different experiments? If yes, was there a similar statistical difference for each individual experiment? Reviewer #2: Jaiswal et al describes the cell autonomous role for Bcl-3 in CD8+T cell differentiation during the response to lymphocytic choriomeningitis virus infection using single-cell RNA-seq and flow cytometric analysis of virus specific Bcl3-/- CD8+T cells. Although this study identify the role of Bcl3 in generation of CD8 memory response, it is not clear as to why bcl3 regulate the generation of MPECs. Whether bsl3 somehow controlling activation induced cell death and therefore as a result a reduced frequency of MPECs were found in bsl3 deficient mice. Authors must address this. In addition, authors should show whether Bsl3-/- cd8 t cells proliferate less both in vitro and in vivo. Authors should also show the expression of perforin, gran B, Tbet, Eomes and other effector molecules of CD8 T cells in wt and Bsl3-/- mice. ********** Part III – Minor Issues: Editorial and Data Presentation Modifications Please use this section for editorial suggestions as well as relatively minor modifications of existing data that would enhance clarity. Reviewer #1: (No Response) Reviewer #2: (No Response) ********** Do you want your identity to be public for this peer review? For information about this choice, including consent withdrawal, please see our Privacy Policy. Reviewer #1: No Reviewer #2: No Figure Files: While revising your submission, please upload your figure files to the Preflight Analysis and Conversion Engine (PACE) digital diagnostic tool, https://pacev2.apexcovantage.com. PACE helps ensure that figures meet PLOS requirements. To use PACE, you must first register as a user. Then, login and navigate to the UPLOAD tab, where you will find detailed instructions on how to use the tool. If you encounter any issues or have any questions when using PACE, please email us at figures@plos.org. Data Requirements: Please note that, as a condition of publication, PLOS' data policy requires that you make available all data used to draw the conclusions outlined in your manuscript. Data must be deposited in an appropriate repository, included within the body of the manuscript, or uploaded as supporting information. This includes all numerical values that were used to generate graphs, histograms etc.. For an example see here on PLOS Biology: http://www.plosbiology.org/article/info%3Adoi%2F10.1371%2Fjournal.pbio.1001908#s5. Reproducibility: To enhance the reproducibility of your results, PLOS recommends that you deposit laboratory protocols in protocols.io, where a protocol can be assigned its own identifier (DOI) such that it can be cited independently in the future. For instructions see http://journals.plos.org/plospathogens/s/submission-guidelines#loc-materials-and-methods
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| Revision 1 |
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Dear Dr. Jaiswal, We are pleased to inform you that your manuscript 'The NF-κB regulator Bcl-3 restricts terminal differentiation and promotes memory cell formation of CD8+ T cells during viral infection' has been provisionally accepted for publication in PLOS Pathogens. Before your manuscript can be formally accepted you will need to complete some formatting changes, which you will receive in a follow up email. A member of our team will be in touch with a set of requests. Please note that your manuscript will not be scheduled for publication until you have made the required changes, so a swift response is appreciated. IMPORTANT: The editorial review process is now complete. PLOS will only permit corrections to spelling, formatting or significant scientific errors from this point onwards. Requests for major changes, or any which affect the scientific understanding of your work, will cause delays to the publication date of your manuscript. Should you, your institution's press office or the journal office choose to press release your paper, you will automatically be opted out of early publication. We ask that you notify us now if you or your institution is planning to press release the article. All press must be co-ordinated with PLOS. Thank you again for supporting Open Access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Rudra Channappanavar, DVM, Ph.D. Guest Editor PLOS Pathogens Volker Thiel Section Editor PLOS Pathogens Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens *********************************************************** Reviewer Comments (if any, and for reference): |
| Formally Accepted |
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Dear Dr. Jaiswal, We are delighted to inform you that your manuscript, "The NF-κB regulator Bcl-3 restricts terminal differentiation and promotes memory cell formation of CD8+ T cells during viral infection," has been formally accepted for publication in PLOS Pathogens. We have now passed your article onto the PLOS Production Department who will complete the rest of the pre-publication process. All authors will receive a confirmation email upon publication. The corresponding author will soon be receiving a typeset proof for review, to ensure errors have not been introduced during production. Please review the PDF proof of your manuscript carefully, as this is the last chance to correct any scientific or type-setting errors. Please note that major changes, or those which affect the scientific understanding of the work, will likely cause delays to the publication date of your manuscript. Note: Proofs for Front Matter articles (Pearls, Reviews, Opinions, etc...) are generated on a different schedule and may not be made available as quickly. Soon after your final files are uploaded, the early version of your manuscript, if you opted to have an early version of your article, will be published online. The date of the early version will be your article's publication date. The final article will be published to the same URL, and all versions of the paper will be accessible to readers. Thank you again for supporting open-access publishing; we are looking forward to publishing your work in PLOS Pathogens. Best regards, Kasturi Haldar Editor-in-Chief PLOS Pathogens orcid.org/0000-0001-5065-158X Michael Malim Editor-in-Chief PLOS Pathogens |
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