Germinal center B cells govern their own fate via antibody feedback

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Germinal center B cells govern their own fate via antibody feedback. / Zhang, Yang; Meyer-Hermann, Michael; George, Laura A; Figge, Marc Thilo; Khan, Mahmood; Goodall, Margaret; Young, Stephen P; Reynolds, Adam; Falciani, Francesco; Waisman, Ari; Notley, Clare A; Ehrenstein, Michael R; Kosco-Vilbois, Marie; Toellner, Kai-Michael.

In: The Journal of Experimental Medicine, Vol. 210, No. 3, 11.03.2013, p. 457-64.

Research output: Contribution to journalArticle

Harvard

Zhang, Y, Meyer-Hermann, M, George, LA, Figge, MT, Khan, M, Goodall, M, Young, SP, Reynolds, A, Falciani, F, Waisman, A, Notley, CA, Ehrenstein, MR, Kosco-Vilbois, M & Toellner, K-M 2013, 'Germinal center B cells govern their own fate via antibody feedback', The Journal of Experimental Medicine, vol. 210, no. 3, pp. 457-64. https://doi.org/10.1084/jem.20120150

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Author

Zhang, Yang ; Meyer-Hermann, Michael ; George, Laura A ; Figge, Marc Thilo ; Khan, Mahmood ; Goodall, Margaret ; Young, Stephen P ; Reynolds, Adam ; Falciani, Francesco ; Waisman, Ari ; Notley, Clare A ; Ehrenstein, Michael R ; Kosco-Vilbois, Marie ; Toellner, Kai-Michael. / Germinal center B cells govern their own fate via antibody feedback. In: The Journal of Experimental Medicine. 2013 ; Vol. 210, No. 3. pp. 457-64.

Bibtex

@article{265e34e825fe4359aae64f4e3cf493b7,
title = "Germinal center B cells govern their own fate via antibody feedback",
abstract = "Affinity maturation of B cells in germinal centers (GCs) is a process of evolution, involving random mutation of immunoglobulin genes followed by natural selection by T cells. Only B cells that have acquired antigen are able to interact with T cells. Antigen acquisition is dependent on the interaction of B cells with immune complexes inside GCs. It is not clear how efficient selection of B cells is maintained while their affinity matures. Here we show that the B cells' own secreted products, antibodies, regulate GC selection by limiting antigen access. By manipulating the GC response with monoclonal antibodies of defined affinities, we show that antibodies in GCs are in affinity-dependent equilibrium with antibodies produced outside and that restriction of antigen access influences B cell selection, seen as variations in apoptosis, plasma cell output, T cell interaction, and antibody affinity. Feedback through antibodies produced by GC-derived plasma cells can explain how GCs maintain an adequate directional selection pressure over a large range of affinities throughout the course of an immune response, accelerating the emergence of B cells of highest affinities. Furthermore, this mechanism may explain how spatially separated GCs communicate and how the GC reaction terminates.",
author = "Yang Zhang and Michael Meyer-Hermann and George, {Laura A} and Figge, {Marc Thilo} and Mahmood Khan and Margaret Goodall and Young, {Stephen P} and Adam Reynolds and Francesco Falciani and Ari Waisman and Notley, {Clare A} and Ehrenstein, {Michael R} and Marie Kosco-Vilbois and Kai-Michael Toellner",
year = "2013",
month = "3",
day = "11",
doi = "10.1084/jem.20120150",
language = "English",
volume = "210",
pages = "457--64",
journal = "The Journal of Experimental Medicine",
issn = "0022-1007",
publisher = "Rockefeller University Press",
number = "3",

}

RIS

TY - JOUR

T1 - Germinal center B cells govern their own fate via antibody feedback

AU - Zhang, Yang

AU - Meyer-Hermann, Michael

AU - George, Laura A

AU - Figge, Marc Thilo

AU - Khan, Mahmood

AU - Goodall, Margaret

AU - Young, Stephen P

AU - Reynolds, Adam

AU - Falciani, Francesco

AU - Waisman, Ari

AU - Notley, Clare A

AU - Ehrenstein, Michael R

AU - Kosco-Vilbois, Marie

AU - Toellner, Kai-Michael

PY - 2013/3/11

Y1 - 2013/3/11

N2 - Affinity maturation of B cells in germinal centers (GCs) is a process of evolution, involving random mutation of immunoglobulin genes followed by natural selection by T cells. Only B cells that have acquired antigen are able to interact with T cells. Antigen acquisition is dependent on the interaction of B cells with immune complexes inside GCs. It is not clear how efficient selection of B cells is maintained while their affinity matures. Here we show that the B cells' own secreted products, antibodies, regulate GC selection by limiting antigen access. By manipulating the GC response with monoclonal antibodies of defined affinities, we show that antibodies in GCs are in affinity-dependent equilibrium with antibodies produced outside and that restriction of antigen access influences B cell selection, seen as variations in apoptosis, plasma cell output, T cell interaction, and antibody affinity. Feedback through antibodies produced by GC-derived plasma cells can explain how GCs maintain an adequate directional selection pressure over a large range of affinities throughout the course of an immune response, accelerating the emergence of B cells of highest affinities. Furthermore, this mechanism may explain how spatially separated GCs communicate and how the GC reaction terminates.

AB - Affinity maturation of B cells in germinal centers (GCs) is a process of evolution, involving random mutation of immunoglobulin genes followed by natural selection by T cells. Only B cells that have acquired antigen are able to interact with T cells. Antigen acquisition is dependent on the interaction of B cells with immune complexes inside GCs. It is not clear how efficient selection of B cells is maintained while their affinity matures. Here we show that the B cells' own secreted products, antibodies, regulate GC selection by limiting antigen access. By manipulating the GC response with monoclonal antibodies of defined affinities, we show that antibodies in GCs are in affinity-dependent equilibrium with antibodies produced outside and that restriction of antigen access influences B cell selection, seen as variations in apoptosis, plasma cell output, T cell interaction, and antibody affinity. Feedback through antibodies produced by GC-derived plasma cells can explain how GCs maintain an adequate directional selection pressure over a large range of affinities throughout the course of an immune response, accelerating the emergence of B cells of highest affinities. Furthermore, this mechanism may explain how spatially separated GCs communicate and how the GC reaction terminates.

U2 - 10.1084/jem.20120150

DO - 10.1084/jem.20120150

M3 - Article

C2 - 23420879

VL - 210

SP - 457

EP - 464

JO - The Journal of Experimental Medicine

JF - The Journal of Experimental Medicine

SN - 0022-1007

IS - 3

ER -