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Skip to main content ADVERTISEMENT NEWS CAREERS COMMENTARY JOURNALS LOG IN BECOME A MEMBER Current Issue First release papers Archive About Submit manuscript GET OUR E-ALERTS Main content starts here HOME SCIENCE VOL. 335, NO. 6066 ASYMMETRIC B CELL DIVISION IN THE GERMINAL CENTER REACTION NO ACCESS REPORT Share on Asymmetric B Cell Division in the Germinal Center Reaction BURTON E. BARNETT, MARIA L. CIOCCA, RADHIKA GOENKA, LISA G. BARNETT, JUNMIN WU, TERRI M. LAUFER, JANIS K. BURKHARDT, MICHAEL P. CANCRO, AND STEVEN L. REINERAuthors Info & Affiliations SCIENCE 15 Dec 2011 Vol 335, Issue 6066 pp. 342-344 DOI: 10.1126/science.1213495 NOTIFICATIONS BOOKMARK CHECK ACCESS Stochastic or Asymmetric Fate Determination? Abstract Supplementary Material References and Notes Information & Authors Metrics & Citations Check Access References Figures Tables Media Share Stochastic or Asymmetric Fate Determination? During an adaptive immune response, B lymphocytes rapidly divide and differentiate into effector cell populations, including antibody-secreting plasmablasts and memory B cells. Many also change the class of antibody they secrete, through a process called isotype switching. During this process, some cells die. Whether cells acquire these different fates in a stochastic or programmed manner, however, is unclear. Duffy et al. (p. 338, published online 5 January) used single-cell tracking to determine the times to division, differentiation into a plasmablast, isotype switching, and death of stimulated B lymphocytes. Statistical analysis and mathematical modeling revealed that these cell-fate decisions appear to be the result of random clocks: Which clock went off first (division, differentiation, or death), determined the fate of the cell. Barnett et al. (p. 342, published online 15 December) sought to determine whether asymmetrical cell division, which is thought to contribute to effector cell-fate decisions in T cells, may be at work in B lymphocytes. Indeed, factors important for the initiation and maintenance of germinal center B lymphocyte identity, along with an ancestral polarity protein, were asymmetrically distributed and maintained their asymmetry during cell division. Abstract Lifelong antibody responses to vaccination require reorganization of lymphoid tissue and dynamic intercellular communication called the germinal center reaction. B lymphocytes undergo cellular polarization during antigen stimulation, acquisition, and presentation, which are critical steps for initiating humoral immunity. Here, we show that germinal center B lymphocytes asymmetrically segregate the transcriptional regulator Bcl6, the receptor for interleukin-21, and the ancestral polarity protein atypical protein kinase C to one side of the plane of division, generating unequal inheritance of fate-altering molecules by daughter cells. Germinal center B lymphocytes from mice with a defect in leukocyte adhesion fail to divide asymmetrically. These results suggest that motile cells lacking constitutive attachment can receive provisional polarity cues from the microenvironment to generate daughter cell diversity and self-renewal. Register and access this article for free As a service to the community, this article is available for free. LOG IN CREATE A FREE ACCOUNT Access the full article View all access options to continue reading this article. CHECK ACCESS ALREADY A SUBSCRIBER OR AAAS MEMBER? SIGN IN AS AN INDIVIDUAL OR VIA YOUR INSTITUTION Supplementary Material File (1213495.barnett.som.pdf) DOWNLOAD 7.51 MB References and Notes 1 MacLennan I. C., Germinal centers. Annu. Rev. Immunol. 12, 117 (1994). CROSSREF PUBMED WEB OF SCIENCE GOOGLE SCHOLAR 2 Nutt S. L., Tarlinton D. M., Germinal center B and follicular helper T cells: Siblings, cousins or just good friends? Nat. Immunol. 12, 472 (2011). CROSSREF PUBMED WEB OF SCIENCE GOOGLE SCHOLAR 3 Qi H., Cannons J. L., Klauschen F., Schwartzberg P. L., Germain R. N., SAP-controlled T-B cell interactions underlie germinal centre formation. Nature 455, 764 (2008). CROSSREF PUBMED WEB OF SCIENCE GOOGLE SCHOLAR 4 Okada T., et al., Antigen-engaged B cells undergo chemotaxis toward the T zone and form motile conjugates with helper T cells. PLoS Biol. 3, e150 (2005). CROSSREF PUBMED WEB OF SCIENCE GOOGLE SCHOLAR 5 Suzuki K., Grigorova I., Phan T. G., Kelly L. M., Cyster J. 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LOG IN TO SUBMIT A RESPONSE Information & Authors Information Published In SCIENCE Volume 335 | Issue 6066 20 January 2012 Copyright Copyright © 2012, American Association for the Advancement of Science. Article versions You are viewing the most recent version of this article. First Release PDF (Version 1) Submission history Received: 2 September 2011 Accepted: 4 November 2011 Published in print: 20 January 2012 Permissions Request permissions for this article. REQUEST PERMISSIONS Acknowledgments We thank J. Chaix, S. Gordon, M. Paley, and L. Rupp for assistance. We are grateful for funding from the NIH (grants AI042370 and AI076458 to S.L.R., T32GM07229 to B.E.B., T32HD007516 and 3T32GM007170-36S1 to M.L.C., T32AI055428 to R.G., and AI065644 to J.K.B.), the U.S. Department of Defense (grant W81WWXWH1010185 to M.P.C.), Veterans Administration (grant BX000435 to T.M.L.), and the Abramson family (to S.L.R.). The data reported in this paper are tabulated in the main paper and in the supporting online material. The authors declare no conflicts of interest. Authors Affiliations Burton E. Barnett Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. View all articles by this author Maria L. Ciocca Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. View all articles by this author Radhika Goenka Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. View all articles by this author Lisa G. Barnett Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. View all articles by this author Junmin Wu Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. View all articles by this author Terri M. Laufer Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA. View all articles by this author Janis K. Burkhardt Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA. View all articles by this author Michael P. Cancro Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. View all articles by this author Steven L. Reiner* [email protected] Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA. Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA. Present address: Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA. View all articles by this author Notes * To whom correspondence should be addressed. E-mail: [email protected] Metrics & Citations Metrics Article Usage Note: The article usage is presented with a three- to four-day delay and will update daily once available. Due to this delay, usage data will not appear immediately following publication. Citation information is sourced from Crossref Cited-by service. 0 citation in Scopus 77 citation in Web of Science Altmetrics Citations Cite as Burton E. Barnett et al. ,Asymmetric B Cell Division in the Germinal Center Reaction.Science335,342-344(2012).DOI:10.1126/science.1213495 Export citation Select the format you want to export the citation of this publication. Please select one from the list RIS (ProCite, Reference Manager) EndNote BibTex Medlars RefWorks DIRECT IMPORT Cited by Steven L. Reiner,Immune regeneration: implications for cancer immunotherapy and beyond, Journal of Clinical Investigation, 135, 13, (2025). https://doi.org/10.1172/JCI192731 CROSSREF Ian R. Tizard,Bovine B cell responses, The Immunology of the Domestic Ruminants, (193-217), (2025). https://doi.org/10.1016/B978-0-443-33572-3.00011-4 CROSSREF Ian R. Tizard,Feline humoral immunity, The Immunology of the Cat, (161-180), (2025). https://doi.org/10.1016/B978-0-443-29178-4.00011-3 CROSSREF D. B. Chudakov,O. A. Shustova,M. A. Streltsova,A. A. Generalov,R. A. Velichinskii,O. D. Kotsareva,G. V. 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