Asymmetric B Cell Division in the Germinal Center Reaction

被引:74
作者
Barnett, Burton E. [1 ,3 ]
Ciocca, Maria L. [1 ,3 ]
Goenka, Radhika [2 ]
Barnett, Lisa G. [3 ]
Wu, Junmin [1 ,3 ]
Laufer, Terri M. [3 ,4 ]
Burkhardt, Janis K. [2 ,5 ]
Cancro, Michael P. [2 ]
Reiner, Steven L. [1 ,3 ]
机构
[1] Univ Penn, Abramson Family Canc Res Inst, Philadelphia, PA 19104 USA
[2] Univ Penn, Perelman Sch Med, Dept Pathol & Lab Med, Philadelphia, PA 19104 USA
[3] Univ Penn, Perelman Sch Med, Dept Med, Philadelphia, PA 19104 USA
[4] Philadelphia Vet Affairs Med Ctr, Philadelphia, PA 19104 USA
[5] Childrens Hosp Philadelphia, Philadelphia, PA 19104 USA
关键词
T-LYMPHOCYTE DIVISION; BCL-6; ANTIGEN; DIFFERENTIATION; INFLAMMATION; EXPRESSION; RESPONSES;
D O I
10.1126/science.1213495
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
引用
收藏
页码:342 / 344
页数:3
相关论文
共 19 条
[1]   Optimal Germinal Center Responses Require a Multistage T Cell:B Cell Adhesion Process Involving Integrins, SLAM-Associated Protein, and CD84 [J].
Cannons, Jennifer L. ;
Qi, Hai ;
Lu, Kristina T. ;
Dutta, Mala ;
Gomez-Rodriguez, Julio ;
Cheng, Jun ;
Wakeland, Edward K. ;
Germain, Ronald N. ;
Schwartzberg, Pamela L. .
IMMUNITY, 2010, 32 (02) :253-265
[2]   Asymmetric T lymphocyte division in the initiation of adaptive immune responses [J].
Chang, John T. ;
Palanivel, Vikram R. ;
Kinjyo, Ichiko ;
Schambach, Felix ;
Intlekofer, Andrew M. ;
Banerjee, Arnob ;
Longworth, Sarah A. ;
Vinup, Kristine E. ;
Mrass, Paul ;
Oliaro, Jane ;
Killeen, Nigel ;
Orange, Jordan S. ;
Russell, Sarah M. ;
Weninger, Wolfgang ;
Reiner, Steven L. .
SCIENCE, 2007, 315 (5819) :1687-1691
[3]   Asymmetric Proteasome Segregation as a Mechanism for Unequal Partitioning of the Transcription Factor T-bet during T Lymphocyte Division [J].
Chang, John T. ;
Ciocca, Maria L. ;
Kinjyo, Ichiko ;
Palanivel, Vikram R. ;
McClurkin, Courtney E. ;
De Jong, Caitlin S. ;
Mooney, Erin C. ;
Kim, Jiyeon S. ;
Steinel, Natalie C. ;
Oliaro, Jane ;
Yin, Catherine C. ;
Florea, Bogdan I. ;
Overkleeft, Herman S. ;
Berg, Leslie J. ;
Russell, Sarah M. ;
Koretzky, Gary A. ;
Jordan, Martha S. ;
Reiner, Steven L. .
IMMUNITY, 2011, 34 (04) :492-504
[4]   Control of inflammation, cytokine expression, and germinal center formation by BCL-6 [J].
Dent, AL ;
Shaffer, AL ;
Yu, X ;
Allman, D ;
Staudt, LM .
SCIENCE, 1997, 276 (5312) :589-592
[5]  
FISCHER A, 1986, J IMMUNOL, V136, P3198
[6]   Transcription factor IRF4 controls plasma cell differentiation and class-switch recombination [J].
Klein, Ulf ;
Casola, Stefano ;
Cattoretti, Giorgio ;
Shen, Qiong ;
Lia, Marie ;
Mo, Tongwei ;
Ludwig, Thomas ;
Rajewsky, Klaus ;
Dalla-Favera, Riccardo .
NATURE IMMUNOLOGY, 2006, 7 (07) :773-782
[7]   Asymmetric cell division: recent developments and their implications for tumour biology [J].
Knoblich, Juergen A. .
NATURE REVIEWS MOLECULAR CELL BIOLOGY, 2010, 11 (12) :849-860
[8]   IL-21 acts directly on B cells to regulate Bcl-6 expression and germinal center responses [J].
Linterman, Michelle A. ;
Beaton, Laura ;
Yu, Di ;
Ramiscal, Roybel R. ;
Srivastava, Monika ;
Hogan, Jennifer J. ;
Verma, Naresh K. ;
Smyth, Mark J. ;
Rigby, Robert J. ;
Vinuesa, Carola G. .
JOURNAL OF EXPERIMENTAL MEDICINE, 2010, 207 (02) :353-363
[9]  
MACLENNAN ICM, 1994, ANNU REV IMMUNOL, V12, P117, DOI 10.1146/annurev.immunol.12.1.117
[10]   Germinal center B and follicular helper T cells: siblings, cousins or just good friends? [J].
Nutt, Stephen L. ;
Tarlinton, David M. .
NATURE IMMUNOLOGY, 2011, 12 (06) :472-477