David Michael Allman, PhD

Professor of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania

Contact InformationDepartment of Pathology and Laboratory Medicine
Perelman School of Medicine at the University of Pennsylvania
John Morgan Building, Rm. 230
3620 Hamilton Walk
Philadelphia, PA 19104
Office: 215-746-5547
Fax: 215-573-2350

Specialty Division

Cancer and Immunobiology

Research Expertise

Research Interests:  Plasma cell differentiation, B cell development

Research Summary:

Our main focus concerns the mechanisms underlying differentiation within the B cell lineage. We are currently focusing on two aspects of B cell development and differentiation.

1) A central interest in my lab concerns the differentiation of antibody-secreting plasma cells from naïve and memory B cells. We are primarily interested in the following questions: a) How long to plasma cells live and what signals regulate their survival? b) Do plasma cells located at sites other than the bone marrow, such as within the gut mucosa, utilize the same survival mechanisms as those in the marrow? c) To what extent does persisting antigen or chronic infection promote lasting antibody responses? d) What are the regulatory networks, transcriptional and otherwise, that underwrite the differentiation of an activated B cell into an antibody-secreting plasma cell?

Background: High-affinity neutralizing antibodies play central roles if combating infections and constitute the chief mechanism underlying the vast majority of effective vaccines. Once induced, antigen-specific antibodies can be found in the serum long after infection or vaccination. A key question in immunology is how this works: Are lasting antibody responses mediated by memory B cells, induced periodically to generate short-lived plasma cells by persisting antigen? Or does the durability of serum antibody titers reflect the activity of long-lived plasma cells?

It is generally accepted that, once generated in peripheral lymphoid tissues, some new plasma cells home to the bone marrow where they survive for months to years in mice, and perhaps decades in people. However, the vast majority of newly generated plasma cells fail to become long-lived. Given that certain vaccines fail to induce long-term protective immunity, it follows that these antigens or immunization strategies fail to induce the formation of long-lived plasma cells. We would like to understand why.

To this end, we are striving to understand the factors underlying plasma cell lifespans, and why some plasma cells become long-lived, while others do not. We are examining this issue on both the cellular and molecular levels. With a cellular perspective, we have developed strategies to identify newly formed versus long-lived plasma cells in the bone marrow. This capacity also allows us to evaluate different types of antigens and immunization strategies for their capacity to induce short- and long-lived plasma cells. From these experiments we have learned that the bone marrow plasma cell pool is exceptionally dynamic, containing large fractions of newly formed plasma cells that must compete effectively for presumably limiting survival niches. Hence we are working to define the components of these niches and determine how to manipulate them. For a molecular perspective, we have also developed genome-wide gene expression data sets for short- and long-lived plasma cells in the bone marrow and in the gut mucosa. These data that have inspired new hypotheses about the biochemical and transcriptional pathways underlying adoption of the plasma cell fate by naïve B cells and the role of mitosis in this process.

In related work, we are focused on elucidating the influence of microbe-lymphocyte interactions in the gastrointestinal tract on systemic immunity, particularly the generation and maintenance of serum IgA responses.

2) The second main focus in my laboratory concerns how specific transcription factors promote the earliest phases of B cell development from multipotent progenitors.

Background: To generate early B-lineage cells, the development of alternative lineages such as T cells, innate lymphoid cells, and myeloid lineage cells must be suppressed. Previous work on this question concentrated heavily on the transcription factor Pax5 and its capacity to both promote B cell differentiation and inhibit alternative fates. However we recently showed that Early B cell Factor-1 (EBF), another transcription factor required for early B lymphopoiesis, both promotes B cell development and represses myeloid and T-lineage development independently of Pax5. Recent work in the lab has shown that EBF accomplishes this task by actively and directly repressing the T cell and innate lymphoid cell-requisite transcription factor Gata3. To test this hypothesis further we developed synthetic Zinc-finger proteins to perturb interactions between EBF and discrete cis elements in the Gata3 locus, and test the impact of these perturbations on early B and T cell development. The latter studies revealed a general strategy for perturbing interactions between known transcription factors and relevant regulatory cis elements in a wide variety of experimental systems; we are applying this general approach to several differentiation pathways including early plasma cell differentiation.

Graduate Groups



BS (Microbiology), Pennsylvania State University, 1982
PhD (Immunology), University of Pennsylvania, 1993

Specialty Certification

Postgraduate Training

I.R.T.A. Fellow, National Institute on Aging, NIH, 1995-96
I.R.T.A. Fellow, National Cancer Institute, NIH, 1995-96
Fellow, Institute for Cancer Center, Fox Chase Cancer Center, 1996-99

Awards and Honors

Edward David Lustbader Prize for Excellence in Research, Fox Chase Cancer Center, 1999
Scholar, Leukemia and Lymphoma Society, 2004-09
Excellence in Teaching Award for Outstanding Instruction in Immunology (Module 1), Perelman School of Medicine at the University of Pennsylvania, 2013
Dean's Award for Excellence in Basic Science Teaching, Perelman School of Medicine at the University of Pennsylvania, 2015

Memberships and Professional Organizations

NIA Site Visit Review Team, 2003
NIH/CSR/NIA-B Study Section, 2003-08
NIH/CSR/IMB Study Section (now CMIB), 2008-12
NIH/CSR CMIB Study Section, 2012-present

Web Links

Selected Publications

Development of an mRNA-lipid nanoparticle vaccine against Lyme disease

Pine M, Arora G, Hart TM, Bettini E, Gaudette BT, Muramatsu H, Tombácz I, Kambayashi T, Tam YK, Brisson D, Allman D, Locci M, Weissman D, Fikrig E, Pardi N. Mol Ther 31(9):2702-2714, Sep 2023. doi: 10.1016/j.ymthe.2023.07.022. Epub 2023 Aug 2. PMID: 37533256; PMCID: PMC10492027.

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IgA deficiency destabilizes homeostasis toward intestinal microbes and increases systemic immune dysregulation

Conrey PE, Denu L, O'Boyle KC, Rozich I, Green J, Maslanka J, Lubin JB, Duranova T, Haltzman BL, Gianchetti L, Oldridge DA, De Luna N, Vella LA, Allman D, Spergel JM, Tanes C, Bittinger K, Henrickson SE, Silverman MA. Sci Immunol 8(83):eade2335, May 2023. doi: 10.1126/sciimmunol.ade2335. Epub 2023 May 26. PMID: 37235682.

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BLyS neutralization results in selective anti-HLA alloantibody depletion without successful desensitization

Agarwal D, Luning Prak ET, Bharani T, Everly M, Migone TS, Cancro M, Allman D, Choe I, Kearns JD, Trofe-Clark J, Naji A, Kamoun M. Transpl Immunol 69:101465. doi: 10.1016/j.trim.2021.101465, Dec 2021. Epub 2021 Sep 10. PMID: 34506905.

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mTORC1 coordinates an immediate unfolded protein response-related transcriptome in activated B cells preceding antibody secretion

Gaudette BT, Jones DD, Bortnick A, Argon Y, Allman DNat Commun 11(1):723, Feb 2020. doi: 10.1038/s41467-019-14032-1. PMID: 32024827; PMCID: PMC7002553.

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Recirculating Intestinal IgA-Producing Cells Regulate Neuroinflammation via IL-10

Rojas OL, Pröbstel AK, Porfilio EA, Wang AA, Charabati M, Sun T, Lee DSW, Galicia G, Ramaglia V, Ward LA, Leung LYT, Najafi G, Khaleghi K, Garcillán B, Li A, Besla R, Naouar I, Cao EY, Chiaranunt P, Burrows K, Robinson HG, Allanach JR, Yam J, Luck H, Campbell DJ, Allman D, Brooks DG, Tomura M, Baumann R, Zamvil SS, Bar-Or A, Horwitz MS, Winer DA, Mortha A, Mackay F, Prat A, Osborne LC, Robbins C, Baranzini SE, Gommerman JL. Cell 176(3):610-624.e18, Jan 2019. doi: 10.1016/j.cell.2018.11.035. Epub 2019 Jan 3. Erratum in: Cell. 2019 Apr 4;177(2):492-493. PMID: 30612739; PMCID: PMC6903689.

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Commensal Microbes Induce Serum IgA Responses that Protect against Polymicrobial Sepsis

Wilmore JR, Gaudette BT, Gomez Atria D, Hashemi T, Jones DD, Gardner CA, Cole SD, Misic AM, Beiting DP, Allman DCell Host Microbe 23(3):302-311.e3, Mar 2018. doi: 10.1016/j.chom.2018.01.005. Epub 2018 Feb 22. PMID: 29478774; PMCID: PMC6350773.

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T Regulatory Cells Support Plasma Cell Populations in the Bone Marrow

Glatman Zaretsky A, Konradt C, Dépis F, Wing JB, Goenka R, Atria DG, Silver JS, Cho S, Wolf AI, Quinn WJ, Engiles JB, Brown DC, Beiting D, Erikson J, Allman D, Cancro MP, Sakaguchi S, Lu LF, Benoist CO, Hunter CA. Cell Rep 18(8):1906-1916, Feb 2017. doi: 10.1016/j.celrep.2017.01.067. PMID: 28228257; PMCID: PMC5361408.

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Cellular Dynamics of Memory B Cell Populations: IgM+ and IgG+ Memory B Cells Persist Indefinitely as Quiescent Cells

Jones DD, Wilmore JR, Allman DJ Immunol 195(10):4753-9, Nov 2015. doi: 10.4049/jimmunol.1501365. Epub 2015 Oct 5. PMID: 26438523; PMCID: PMC4637268.

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Lasting antibody responses are mediated by a combination of newly formed and established bone marrow plasma cells drawn from clonally distinct precursors

Chernova I, Jones DD, Wilmore JR, Bortnick A, Yucel M, Hershberg U, Allman DJ Immunol 193(10):4971-9, Nov 2014. doi: 10.4049/jimmunol.1401264. Epub 2014 Oct 17. PMID: 25326027; PMCID: PMC4234148.

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Transcriptional repression of Gata3 is essential for early B cell commitment

Banerjee A, Northrup D, Boukarabila H, Jacobsen SE, Allman DImmunity 38(5):930-42, May 2013. doi: 10.1016/j.immuni.2013.01.014. Epub 2013 May 16. PMID: 23684985; PMCID: PMC3664383.

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