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Science 335 (6066): 342-344

Copyright © 2012 by the American Association for the Advancement of Science

Asymmetric B Cell Division in the Germinal Center Reaction

Burton E. Barnett,1,3 Maria L. Ciocca,1,3 Radhika Goenka,2 Lisa G. Barnett,3 Junmin Wu,1,3 Terri M. Laufer,3,4 Janis K. Burkhardt,2,5 Michael P. Cancro,2 Steven L. Reiner1,3,*,{dagger}

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.

1 Abramson Family Cancer Research Institute, University of Pennsylvania, Philadelphia, PA 19104, USA.
2 Department of Pathology and Laboratory Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
3 Department of Medicine, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA 19104, USA.
4 Philadelphia Veterans Affairs Medical Center, Philadelphia, PA 19104, USA.
5 Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA.

{dagger} Present address: Department of Microbiology and Immunology and Department of Pediatrics, College of Physicians and Surgeons of Columbia University, New York, NY 10032, USA.

* To whom correspondence should be addressed. E-mail: sreiner{at}columbia.edu

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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Y. Wine, D. R. Boutz, J. J. Lavinder, A. E. Miklos, R. A. Hughes, K. H. Hoi, S. T. Jung, A. P. Horton, E. M. Murrin, A. D. Ellington, et al. (2013)
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Cutting Edge: Asymmetric Memory T Cell Division in Response to Rechallenge.
M. L. Ciocca, B. E. Barnett, J. K. Burkhardt, J. T. Chang, and S. L. Reiner (2012)
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