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Ann M Haberman PhD

Assistant Professor of Laboratory Medicine and of Immunobiology; Director, In Vivo Imaging Facility

Research Interests

B lymphocytes; Germinal center formation; Cell migration in vivo; Two-photon laser scanning microscopy


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 migratory behavior of activated B cells 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 influencing the delayed onset of germinal center formation. I am also interested in the events that influence the further differentiation of germinal center B cells toward a phenotype of long-term plasma cells and memory cells that are critical for long-term resistance to pathogens.

Extensive Research Description

My research focuses on the cellular and molecular interactions regulating the form and function of an inducible lymphoid tissue structure called germinal centers. Germinal centers (GC) develop in the center of B cell follicles in spleen and lymph nodes about one week after initial immunization. GCs are sites of extreme metabolism, with very high proliferation and death rates, and evolve over time to form structures with phenotypically distinct zones (Fig 1). GC development requires the intricate interactions of B cells with multiple other cell types to achieve both the affinity maturation of immunoglobulin and the generation of memory B cells that are key to long-term immune protection. My research employs two-photon laser scanning microscopy to image the movement of GC B cells in vivo. This powerful technique allows researchers to observe and track the movement of fluorescently labeled cells over time in vivo as they interact and respond to their environment. Application of this technique has allowed us to define migration patterns of B cells responding to immunization within GCs that suggest that the two major compartments of GCs are functionally independent.The GC response remains poorly understood, however, in part because of its complexity, and major questions remain unresolved. Defining the timing and location of critical interactions between B and other cell types, such as T cells, dendritic cells and macrophages, will be an essential component of advances in this field. Using a variety of techniques, we hope to tease apart the role that each of these cellular interactions play in the cascade of events regulating this rapidly proliferating aggregate of responding B cells.


Selected Publications

  • Rompolas P, Deschene ER, Zito G, Gonzalez DG, Saotome I, Haberman AM, and Greco V (2012) Live imaging of stem cell and progeny behaviour in physiological hair-follicle regeneration. Nature 487:496-499
  • King IL, Fortier A, Tighe M, Dibble J, Watts GF, Veerapen N, Haberman AM, Besra GS, Mohrs M, Brenner MB, and Leadbetter EA (2012) Invariant natural killer T cells direct B cell responses to cognate lipid antigen in an IL-21-dependent manner. Nat Immunol 13:44-50
  • Esplugues E, Huber S, Gagliani N, Hauser AE, Town T, Wan YY, O'Connor W, Jr., Rongvaux A, Van Rooijen N, Haberman AM, Iwakura Y, Kuchroo VK, Kolls JK, Bluestone JA, Herold KC, and Flavell RA (2011) Control of TH17 cells occurs in the small intestine. Nature 475:514-518
  • Eisenbarth SC, Williams A, Colegio OR, Meng H, Strowig T, Rongvaux A, Henao-Mejia J, Thaiss CA, Joly S, Gonzalez DG, Xu L, Zenewicz LA, Haberman AM, Elinav E, Kleinstein SH, Sutterwala FS, and Flavell RA (2012) NLRP10 is a NOD-like receptor essential to initiate adaptive immunity by dendritic cells. Nature 484:510-513
  • Bockenstedt LK, Gonzalez DG, Haberman AM, and Belperron AA (2012) Spirochete antigens persist near cartilage after murine Lyme borreliosis therapy. J Clin Invest 122:2652-2660
  • Kerfoot SM, Yaari G, Patel JR, Johnson KL, Gonzalez D, Kleinstein SH, and Haberman AM (June 2011) Germinal center B cell and T follicular helper cell development initiates in the interfollicular zone. Immunity, 34(6) 947-60.
  • Hauser AE, Kerfoot SM, and Haberman AM (2010). Cellular choreography in the germinal center: new visions from in vivo imaging. Seminars in Immunopathology, 3,239-255
  • Hauser AE, Shlomchik MJ, and Haberman AM (2007). In vivo imaging studies shed light on germinal centre development. Nature Review Immunology, 7, 499-504
  • Hauser AE, Junt T, Mempel TR, Sneddon MW, Kleinstein SH, Henrickson SE, von Andrian UH, Shlomchik MJ, and Haberman AM (2007). Definition of germinal center B migration In vivo reveals predominant intra-zonal circulation patterns. Immunity, 26, 655-667
  • Haberman AM, Shlomchik MJ (Sep 2003) Reassessing the function of immune-complex retention by follicular dendritic cells. Nature Review Immunology, 3(9)757-64

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