Differential organization of tonic and chronic B cell antigen receptors in the plasma membrane

被引:47
作者
de Castro, Maria Angela Gomes [1 ]
Wildhagen, Hanna [1 ]
Sograte-Idrissi, Shama [1 ,2 ]
Hitzing, Christoffer [3 ]
Binder, Mascha [4 ]
Trepel, Martin [4 ,5 ]
Engels, Niklas [3 ]
Opazo, Felipe [1 ,2 ]
机构
[1] Univ Med Ctr Gottingen, Inst Neuro & Sensory Physiol, Humboldtallee 23, D-37073 Gottingen, Germany
[2] Univ Gottingen, Ctr Biostruct Imaging Neurodegenerat BIN, Med Ctr, Von Siebold Str 3a, D-37075 Gottingen, Germany
[3] Univ Med Ctr Gottingen, Inst Cellular & Mol Immunol, Humboldtallee 34, D-37073 Gottingen, Germany
[4] Univ Med Ctr Hamburg Eppendorf, BMT Sect Pneumol, Dept Oncol & Hematol, Martinistr 52, D-20246 Hamburg, Germany
[5] Augsburg Med Ctr, Dept Hematol & Oncol, Stenglinstr 2, D-86156 Augsburg, Germany
关键词
INTERNAL-REFLECTION FLUORESCENCE; SUPERRESOLUTION MICROSCOPY; IMMUNOGLOBULIN; ARTIFACTS; LYMPHOCYTES; INITIATION; COMPLEXES; PROTEINS; DYNAMICS; SURVIVAL;
D O I
10.1038/s41467-019-08677-1
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
Stimulation of the B cell antigen receptor (BCR) triggers signaling pathways that promote the differentiation of B cells into plasma cells. Despite the pivotal function of BCR in B cell activation, the organization of the BCR on the surface of resting and antigen-activated B cells remains unclear. Here we show, using STED super-resolution microscopy, that IgM-containing BCRs exist predominantly as monomers and dimers in the plasma membrane of resting B cells, but form higher oligomeric clusters upon stimulation. By contrast, a chronic lymphocytic leukemia-derived BCR forms dimers and oligomers in the absence of a stimulus, but a single amino acid exchange reverts its organization to monomers in unstimulated B cells. Our super-resolution microscopy approach for quantitatively analyzing cell surface proteins may thus help reveal the nanoscale organization of immunoreceptors in various cell types.
引用
收藏
页数:11
相关论文
共 65 条
[1]   Identification of clustering artifacts in photoactivated localization microscopy [J].
Annibale, Paolo ;
Vanni, Stefano ;
Scarselli, Marco ;
Rothlisberger, Ursula ;
Radenovic, Aleksandra .
NATURE METHODS, 2011, 8 (07) :527-528
[2]  
Axelrod D, 2003, METHOD ENZYMOL, V361, P1
[3]   TOTAL INTERNAL-REFLECTION FLUORESCENCE [J].
AXELROD, D ;
BURGHARDT, TP ;
THOMPSON, NL .
ANNUAL REVIEW OF BIOPHYSICS AND BIOENGINEERING, 1984, 13 :247-268
[4]   CLL B-cell receptors can recognize themselves: alternative epitopes and structural clues for autostimulatory mechanisms in CLL [J].
Binder, Mascha ;
Mueller, Fabian ;
Frick, Mareike ;
Wehr, Claudia ;
Simon, Frederic ;
Leistler, Bernd ;
Veelken, Hendrik ;
Mertelsmann, Roland ;
Trepel, Martin .
BLOOD, 2013, 121 (01) :239-241
[5]   Monomeric TCRs drive T cell antigen recognition [J].
Brameshuber, Mario ;
Kellner, Florian ;
Rossboth, Benedikt K. ;
Ta, Haisen ;
Alge, Kevin ;
Sevcsik, Eva ;
Goehring, Janett ;
Axmann, Markus ;
Baumgart, Florian ;
Gascoigne, Nicholas R. J. ;
Davis, Simon J. ;
Stockinger, Hannes ;
Schuetz, Gerhard J. ;
Huppa, Johannes B. .
NATURE IMMUNOLOGY, 2018, 19 (05) :487-+
[6]   Artifacts in single-molecule localization microscopy [J].
Burgert, Anne ;
Letschert, Sebastian ;
Doose, Soeren ;
Sauer, Markus .
HISTOCHEMISTRY AND CELL BIOLOGY, 2015, 144 (02) :123-131
[7]   THE B-CELL ANTIGEN RECEPTOR - STRUCTURE AND FUNCTION OF PRIMARY, SECONDARY, TERTIARY AND QUATERNARY COMPONENTS [J].
CAMBIER, JC ;
BEDZYK, W ;
CAMPBELL, K ;
CHIEN, N ;
FRIEDRICH, J ;
HARWOOD, A ;
JENSEN, W ;
PLEIMAN, C ;
CLARK, MR .
IMMUNOLOGICAL REVIEWS, 1993, 132 :85-106
[8]   Chronic active B-cell-receptor signalling in diffuse large B-cell lymphoma [J].
Davis, R. Eric ;
Ngo, Vu N. ;
Lenz, Georg ;
Tolar, Pavel ;
Young, Ryan M. ;
Romesser, Paul B. ;
Kohlhammer, Holger ;
Lamy, Laurence ;
Zhao, Hong ;
Yang, Yandan ;
Xu, Weihong ;
Shaffer, Arthur L. ;
Wright, George ;
Xiao, Wenming ;
Powell, John ;
Jiang, Jian-Kang ;
Thomas, Craig J. ;
Rosenwald, Andreas ;
Ott, German ;
Muller-Hermelink, Hans Konrad ;
Gascoyne, Randy D. ;
Connors, Joseph M. ;
Johnson, Nathalie A. ;
Rimsza, Lisa M. ;
Campo, Elias ;
Jaffe, Elaine S. ;
Wilson, Wyndham H. ;
Delabie, Jan ;
Smeland, Erlend B. ;
Fisher, Richard I. ;
Braziel, Rita M. ;
Tubbs, Raymond R. ;
Cook, J. R. ;
Weisenburger, Dennis D. ;
Chan, Wing C. ;
Pierce, Susan K. ;
Staudt, Louis M. .
NATURE, 2010, 463 (7277) :88-U97
[10]  
DRAKE JR, 1989, J IMMUNOL, V143, P1768