Irina Grigorova, PhD
09/1993-01/1999 MS, Physics, Specialization in Biophysics, Moscow State University of M.V.Lomonosov, Moscow, Russian Federation
09/1999-12/2005 PhD, Biophysics, University of California San Francisco, San Francisco, California
09/2010-08/2019 Assistant Professor in Microbiology and Immunology, University of Michigan - Ann Arbor, Michigan
09/2010-08/2019 Associate Professor in Microbiology and Immunology, University of Michigan - Ann Arbor, Michigan
The mammalian immune system has evolved to respond to a variety of infectious agents by integrating "danger signals" into distinct signaling outcomes and thus distinct dynamics of intercellular interactions. When the immune response is successful, disease eradication occurs. Our research interests are directed at understanding the quantitative principles that underlie this "signal processing" in an adaptive immune response, specifically in the T-dependent B cell response.
Proper regulation of T-dependent B cell responses is critical for our ability to generate long-term high affinity antibodies (Abs) against multiple pathogens. At the same time, disregulation of B cell responses can lead to development of autoimmunity and cancer. T-dependent immune response is a complex multistep process, where acquisition of antigen and T cell help may lead to B cell activation and differentiation into short-lived antibody-secreting plasma cells and/or germinal center B cells that in turn may give rise to high-affinity long-lived memory B cells and plasma cells. The goal of our research is to understand various factors that affect 1) B cell recruitment into T-dependent response, 2) B cell selection in Germinal Centers into long-lived memory B cells and plasma cells, 3) control of self-reactive B cells, and to assess the role of these factors in vaccines, autoimmune disorders and B cell lymphomas. In the lab we utilize a combination of standard immunological methods, confocal and two-photon intravital microscopy (that enables imaging cell migration and interactions in the lymph nodes of living mice) and systems biology approaches.
In the recent studies we have addressed how the timing of antigen-dependent activation and T cell help affects:
- B cell recruitment in T-dependent immune response
- B cell entry into Germinal Center response
- B cell selection within Germinal Centers and differentiation into plasma cells
- We have also addressed control of Germinal Centers by follicular regulatory T cells (Tfr).
Research Opportunities for Rotating Students
Turner JS, Ke F, Grigorova IL. B Cell Receptor Crosslinking Augments Germinal Center B Cell Selection when T Cell Help Is Limiting. Cell Rep. 2018 Nov 6;25(6):1395-1403.e4. doi: 10.1016/j.celrep.2018.10.042.
Benet ZL, Marthi M, Ke F, Wu R, Turner JS, Gabayre JB, Ivanitskiy MI, Sethi SS, Grigorova IL. CCL3 Promotes Germinal Center B Cells Sampling by Follicular Regulatory T Cells in Murine Lymph Nodes. Front Immunol. 2018 Sep 13;9:2044. doi: 10.3389/fimmu.2018.02044. eCollection 2018.
Wolf SJ, Theros J, Reed TJ, Liu J, Grigorova IL, Martínez-Colón G, Jacob CO, Hodgin JB, Kahlenberg JM. TLR7-Mediated Lupus Nephritis Is Independent of Type I IFN Signaling. J Immunol. 2018 Jul 15;201(2):393-405.
Turner JS, Benet ZL, Grigorova I. Transiently antigen primed B cells can generate multiple subsets of memory cells. PLoS One. 2017 Aug 29;12(8):e0183877.
Turner JS, Benet ZL, Grigorova IL. Antigen Acquisition Enables Newly Arriving B Cells To Enter Ongoing Immunization-Induced Germinal Centers. J Immunol. 2017 Aug 15;199(4):1301-1307.
Turner JS, Marthi M, Benet ZL, Grigorova I. Transiently antigen-primed B cells return to naive-like state in absence of T-cell help. Nat Commun. 2017 Apr 21;8:15072.
Arnon TI, Horton RM, Grigorova IL, Cyster JG. Visualization of splenic marginal zone B-cell shuttling and follicular B-cell egress. Nature. 2013 Jan 31;493(7434):684-8.
Grigorova I, Panteleev M, Cyster JG. Lymph node cortical sinus organization and relationship to lymphocyte egress dynamics and antigen exposure. PNAS 2010
Suzuki K, Grigorova I, Phan TG, Kelly L, Cyster JG, 2009. Visualizing B cell capture of cognate antigen from follicular dendritic cells. J Exp Med, 2009 Jun 8.
Grigorova IL, Schwab SR, Phan TG, Pham TH, Okada T, Cyster JG, 2009. Cortical sinus probing, S1P1-dependent entry and flow-based capture of egressing T cells. Nat Immunol. Jan;10(1):58-65.
Woolf E, Grigorova I, Sagiv A, Grabovsky V, Feigelson SW, Shulman Z, Hartmann T, Sixt M, Cyster JG, Alon R, 2007. Lymph node chemokines promote sustained T lymphocyte motility without triggering stable integrin adhesiveness in the absence of shear forces. Nat Immunol. Oct;8(10):1076-85.