Ann Haberman, PhD
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Research Summary
I am interested in understanding the factors that influence the proliferation, migration and differentiation of germinal center B lymphocytes. A particular interest of mine is the behavior of activated B cells and their interaction with other cell types within the context of tissue architecture. I use a combination of histology, flow cytometry and intravital multiphoton microscopy to study the factors that regulate B cell subset activation and their movements in vivo. A related area of interest includes the cellular interactions of B cells with stromal cells during adaptive immune responses.
Extensive Research Description
My research has focused on the cellular and molecular interactions regulating the form and function of an inducible lymphoid tissue structure called germinal centers. Germinal centers (GC) are large aggregates of B cells specificially responding to a foreign substance. They develop in the center of B cell follicles in spleen and lymph nodes about one week after initial immunization or exposure to pathogens. GCs are sites of extreme metabolism, with very high proliferation and death rates, and evolve over time to form structures with phenotypically distinct zones. GC development requires intricate interactions of B cells with multiple other cell types to achieve both the affinity maturation of plasma cells producing antibodies and the generation of memory B cells that are key to long-term immune protection. The regional composition of other cell types can vary tremendously and can include CD4+ T cell subsets, dendritic cells and activated macrophages. Defining the impact of interactions with other adjacent cell types will be an essential component of advances in this field. My current research aims to tease apart the role that each may play in the cascade of events regulating both the expansion of GC B cells and the effector output of germinal centers.
Coauthors
Research Interests
Antibody Formation; Immunity, Cellular; Lymphocyte Activation; Lymphoid Tissue; Lymphoma, B-Cell; Germinal Center; Dendritic Cells, Follicular; Immunological Synapses
Public Health Interests
Immunology
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Selected Publications
- In vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host diseaseMorin-Zorman S, Wysocki C, Zhu J, Li H, Zorman S, Matte-Martone C, Kisanga E, McNiff J, Jain D, Gonzalez D, Rothstein DM, Lakkis FG, Haberman A, Shlomchik WD. In vivo dynamics of T cells and their interactions with dendritic cells in mouse cutaneous graft-versus-host disease Blood Advances 2019, 3: 2082-2092. PMID: 31296496, PMCID: PMC6650737, DOI: 10.1182/bloodadvances.2019000227.
- Germinal center B cell initiation, GC maturation, and the coevolution of its stromal cell nichesHaberman AM, Gonzalez DG, Wong P, Zhang T, Kerfoot SM. Germinal center B cell initiation, GC maturation, and the coevolution of its stromal cell niches Immunological Reviews 2019, 288: 10-27. PMID: 30874342, PMCID: PMC10234181, DOI: 10.1111/imr.12731.
- Nonredundant Roles of IL-21 and IL-4 in the Phased Initiation of Germinal Center B Cells and Subsequent Self-Renewal Transitions.Gonzalez DG, Cote CM, Patel JR, Smith CB, Zhang Y, Nickerson KM, Zhang T, Kerfoot SM, Haberman AM. Nonredundant Roles of IL-21 and IL-4 in the Phased Initiation of Germinal Center B Cells and Subsequent Self-Renewal Transitions. The Journal Of Immunology 2018, 201: 3569-3579. PMID: 30446568, PMCID: PMC6289626, DOI: 10.4049/jimmunol.1500497.
- Histone demethylase LSD1 is required for germinal center formation and BCL6-driven lymphomagenesisHatzi K, Geng H, Doane AS, Meydan C, LaRiviere R, Cardenas M, Duy C, Shen H, Vidal MNC, Baslan T, Mohammad HP, Kruger RG, Shaknovich R, Haberman AM, Inghirami G, Lowe SW, Melnick AM. Histone demethylase LSD1 is required for germinal center formation and BCL6-driven lymphomagenesis Nature Immunology 2018, 20: 86-96. PMID: 30538335, PMCID: PMC6294324, DOI: 10.1038/s41590-018-0273-1.
- Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell helpZhang TT, Gonzalez DG, Cote CM, Kerfoot SM, Deng S, Cheng Y, Magari M, Haberman AM. Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help ELife 2017, 6: e19552. PMID: 28498098, PMCID: PMC5429091, DOI: 10.7554/elife.19552.
- Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live micePark S, Gonzalez DG, Guirao B, Boucher JD, Cockburn K, Marsh ED, Mesa KR, Brown S, Rompolas P, Haberman AM, Bellaïche Y, Greco V. Tissue-scale coordination of cellular behaviour promotes epidermal wound repair in live mice Nature Cell Biology 2017, 19: 155-163. PMID: 28248302, PMCID: PMC5581297, DOI: 10.1038/ncb3472.
- Preclinical Advances with Multiphoton Microscopy in Live Imaging of Skin CancersSun TY, Haberman AM, Greco V. Preclinical Advances with Multiphoton Microscopy in Live Imaging of Skin Cancers Journal Of Investigative Dermatology 2016, 137: 282-287. PMID: 27847119, PMCID: PMC5258832, DOI: 10.1016/j.jid.2016.08.033.
- Intravital imaging of hair follicle regeneration in the mousePineda CM, Park S, Mesa KR, Wolfel M, Gonzalez DG, Haberman AM, Rompolas P, Greco V. Intravital imaging of hair follicle regeneration in the mouse Nature Protocols 2015, 10: 1116-1130. PMID: 26110716, PMCID: PMC4632978, DOI: 10.1038/nprot.2015.070.
- Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell poolMesa KR, Rompolas P, Zito G, Myung P, Sun TY, Brown S, Gonzalez DG, Blagoev KB, Haberman AM, Greco V. Niche-induced cell death and epithelial phagocytosis regulate hair follicle stem cell pool Nature 2015, 522: 94-97. PMID: 25849774, PMCID: PMC4457634, DOI: 10.1038/nature14306.
- The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal CentersHuang C, Gonzalez DG, Cote CM, Jiang Y, Hatzi K, Teater M, Dai K, Hla T, Haberman AM, Melnick A. The BCL6 RD2 Domain Governs Commitment of Activated B Cells to Form Germinal Centers Cell Reports 2014, 8: 1497-1508. PMID: 25176650, PMCID: PMC4163070, DOI: 10.1016/j.celrep.2014.07.059.
- Dynamic Expression of BCL6 in Murine Conventional Dendritic Cells during In Vivo Development and ActivationZhang TT, Liu D, Calabro S, Eisenbarth SC, Cattoretti G, Haberman AM. Dynamic Expression of BCL6 in Murine Conventional Dendritic Cells during In Vivo Development and Activation PLOS ONE 2014, 9: e101208. PMID: 24979752, PMCID: PMC4076320, DOI: 10.1371/journal.pone.0101208.
- What ticks do under your skin: two-photon intravital imaging of Ixodes scapularis feeding in the presence of the lyme disease spirochete.Bockenstedt LK, Gonzalez D, Mao J, Li M, Belperron AA, Haberman A. What ticks do under your skin: two-photon intravital imaging of Ixodes scapularis feeding in the presence of the lyme disease spirochete. The Yale Journal Of Biology And Medicine 2014, 87: 3-13. PMID: 24600332, PMCID: PMC3941458.
- In vivo imaging of virological synapsesSewald X, Gonzalez DG, Haberman AM, Mothes W. In vivo imaging of virological synapses Nature Communications 2012, 3: 1320. PMID: 23271654, PMCID: PMC3784984, DOI: 10.1038/ncomms2338.
- Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapyPark J, Wrzesinski SH, Stern E, Look M, Criscione J, Ragheb R, Jay SM, Demento SL, Agawu A, Licona Limon P, Ferrandino AF, Gonzalez D, Habermann A, Flavell RA, Fahmy TM. Combination delivery of TGF-β inhibitor and IL-2 by nanoscale liposomal polymeric gels enhances tumour immunotherapy Nature Materials 2012, 11: 895-905. PMID: 22797827, PMCID: PMC3601683, DOI: 10.1038/nmat3355.
- Live imaging of stem cell and progeny behaviour in physiological hair-follicle regenerationRompolas P, Deschene ER, Zito G, Gonzalez DG, Saotome I, Haberman AM, Greco V. Live imaging of stem cell and progeny behaviour in physiological hair-follicle regeneration Nature 2012, 487: 496-499. PMID: 22763436, PMCID: PMC3772651, DOI: 10.1038/nature11218.
- Spirochete antigens persist near cartilage after murine Lyme borreliosis therapyBockenstedt LK, Gonzalez DG, Haberman AM, Belperron AA. Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy Journal Of Clinical Investigation 2012, 122: 2652-2660. PMID: 22728937, PMCID: PMC3386809, DOI: 10.1172/jci58813.
- ProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and PlateletsTruman LA, Bentley KL, Smith EC, Massaro SA, Gonzalez DG, Haberman AM, Hill M, Jones D, Min W, Krause DS, Ruddle NH. ProxTom Lymphatic Vessel Reporter Mice Reveal Prox1 Expression in the Adrenal Medulla, Megakaryocytes, and Platelets American Journal Of Pathology 2012, 180: 1715-1725. PMID: 22310467, PMCID: PMC3349900, DOI: 10.1016/j.ajpath.2011.12.026.
- Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent mannerKing IL, Fortier A, Tighe M, Dibble J, Watts GF, Veerapen N, Haberman AM, Besra GS, Mohrs M, Brenner MB, Leadbetter EA. Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner Nature Immunology 2011, 13: 44-50. PMID: 22120118, PMCID: PMC3833037, DOI: 10.1038/ni.2172.
- Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular ZoneKerfoot SM, Yaari G, Patel JR, Johnson KL, Gonzalez DG, Kleinstein SH, Haberman AM. Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular Zone Immunity 2011, 34: 947-960. PMID: 21636295, PMCID: PMC3280079, DOI: 10.1016/j.immuni.2011.03.024.
- Activated germinal centre B cells undergo directed migration.O'Connor MJ, Hauser AE, Haberman AM, Kleinstein SH. Activated germinal centre B cells undergo directed migration. International Journal Of Data Mining And Bioinformatics 2011, 5: 321-31. PMID: 21805826, PMCID: PMC4343311, DOI: 10.1504/ijdmb.2011.040387.
- Differential Localization of Effector and Memory CD8 T Cell Subsets in Lymphoid Organs during Acute Viral InfectionJung YW, Rutishauser RL, Joshi NS, Haberman AM, Kaech SM. Differential Localization of Effector and Memory CD8 T Cell Subsets in Lymphoid Organs during Acute Viral Infection The Journal Of Immunology 2010, 185: 5315-5325. PMID: 20921525, PMCID: PMC4267692, DOI: 10.4049/jimmunol.1001948.
- Cellular choreography in the germinal center: new visions from in vivo imagingHauser AE, Kerfoot SM, Haberman AM. Cellular choreography in the germinal center: new visions from in vivo imaging Seminars In Immunopathology 2010, 32: 239-255. PMID: 20614218, PMCID: PMC3659422, DOI: 10.1007/s00281-010-0214-z.
- Taking Advantage: High-Affinity B Cells in the Germinal Center Have Lower Death Rates, but Similar Rates of Division, Compared to Low-Affinity CellsAnderson SM, Khalil A, Uduman M, Hershberg U, Louzoun Y, Haberman AM, Kleinstein SH, Shlomchik MJ. Taking Advantage: High-Affinity B Cells in the Germinal Center Have Lower Death Rates, but Similar Rates of Division, Compared to Low-Affinity Cells The Journal Of Immunology 2009, 183: 7314-7325. PMID: 19917681, PMCID: PMC4106706, DOI: 10.4049/jimmunol.0902452.
- Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infectionLee HK, Zamora M, Linehan MM, Iijima N, Gonzalez D, Haberman A, Iwasaki A. Differential roles of migratory and resident DCs in T cell priming after mucosal or skin HSV-1 infection Journal Of Experimental Medicine 2009, 206: 359-370. PMID: 19153243, PMCID: PMC2646574, DOI: 10.1084/jem.20080601.
- New markers for murine memory B cells that define mutated and unmutated subsetsAnderson SM, Tomayko MM, Ahuja A, Haberman AM, Shlomchik MJ. New markers for murine memory B cells that define mutated and unmutated subsets Journal Of Experimental Medicine 2007, 204: 2103-2114. PMID: 17698588, PMCID: PMC2118690, DOI: 10.1084/jem.20062571.
- In vivo imaging studies shed light on germinal-centre developmentHauser AE, Shlomchik MJ, Haberman AM. In vivo imaging studies shed light on germinal-centre development Nature Reviews Immunology 2007, 7: 499-504. PMID: 17589541, DOI: 10.1038/nri2120.
- Definition of Germinal-Center B Cell Migration In Vivo Reveals Predominant Intrazonal Circulation PatternsHauser AE, Junt T, Mempel TR, Sneddon MW, Kleinstein SH, Henrickson SE, von Andrian UH, Shlomchik MJ, Haberman AM. Definition of Germinal-Center B Cell Migration In Vivo Reveals Predominant Intrazonal Circulation Patterns Immunity 2007, 26: 655-667. PMID: 17509908, DOI: 10.1016/j.immuni.2007.04.008.
- Reassessing the function of immune-complex retention by follicular dendritic cellsHaberman AM, Shlomchik MJ. Reassessing the function of immune-complex retention by follicular dendritic cells Nature Reviews Immunology 2003, 3: 757-764. PMID: 12949499, DOI: 10.1038/nri1178.
- Rheumatoid Factors in Health and Disease: Structure, Function, Induction and RegulationHaberman AM, William J, Euler C, Shlomchik MJ. Rheumatoid Factors in Health and Disease: Structure, Function, Induction and Regulation 2003, 6: 169-195. PMID: 12408052, DOI: 10.1159/000066861.
- Very Low Affinity B Cells Form Germinal Centers, Become Memory B Cells, and Participate in Secondary Immune Responses When Higher Affinity Competition Is ReducedDal Porto JM, Haberman AM, Kelsoe G, Shlomchik MJ. Very Low Affinity B Cells Form Germinal Centers, Become Memory B Cells, and Participate in Secondary Immune Responses When Higher Affinity Competition Is Reduced Journal Of Experimental Medicine 2002, 195: 1215-1221. PMID: 11994427, PMCID: PMC2193705, DOI: 10.1084/jem.20011550.
- Germinal Center Initiation, Variable Gene Region Hypermutation, and Mutant B Cell Selection without Detectable Immune Complexes on Follicular Dendritic CellsHannum L, Haberman A, Anderson S, Shlomchik M. Germinal Center Initiation, Variable Gene Region Hypermutation, and Mutant B Cell Selection without Detectable Immune Complexes on Follicular Dendritic Cells Journal Of Experimental Medicine 2000, 192: 931-942. PMID: 11015435, PMCID: PMC2193308, DOI: 10.1084/jem.192.7.931.
- A B-cell receptor-specific selection step governs immature to mature B cell differentiationLevine M, Haberman A, Sant'Angelo D, Hannum L, Cancro M, Janeway C, Shlomchik M. A B-cell receptor-specific selection step governs immature to mature B cell differentiation Proceedings Of The National Academy Of Sciences Of The United States Of America 2000, 97: 2743-2748. PMID: 10688906, PMCID: PMC16000, DOI: 10.1073/pnas.050552997.
- A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine LupusChan O, Hannum L, Haberman A, Madaio M, Shlomchik M. A Novel Mouse with B Cells but Lacking Serum Antibody Reveals an Antibody-independent Role for B Cells in Murine Lupus Journal Of Experimental Medicine 1999, 189: 1639-1648. PMID: 10330443, PMCID: PMC2193634, DOI: 10.1084/jem.189.10.1639.