Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

Ting Ting Zhang; David G. Gonzalez; Christine M. Cote; Steven M. Kerfoot; Shaoli Deng; Yuqing Cheng; Masaki Magari; Ann M. Haberman

doi:10.7554/eLife.19552

Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

Ting Ting Zhang, David G. Gonzalez, Christine M. Cote, Steven M. Kerfoot, Shaoli Deng, Yuqing Cheng, Masaki Magari, Ann M. Haberman

Research output: Contribution to journal › Article › peer-review

42 Citations (Scopus)

Abstract

To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6^hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6^hi follicular state is promoted by a regional and transient diminution of T cell help.

Original language	English
Article number	e19552
Journal	eLife
Volume	6
DOIs	https://doi.org/10.7554/eLife.19552
Publication status	Published - May 12 2017

ASJC Scopus subject areas

Neuroscience(all)
Immunology and Microbiology(all)
Biochemistry, Genetics and Molecular Biology(all)

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10.7554/eLife.19552

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@article{84751e6bf2b846ebb3b054335ea0dd94,

title = "Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help",

abstract = "To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.",

author = "Zhang, {Ting Ting} and Gonzalez, {David G.} and Cote, {Christine M.} and Kerfoot, {Steven M.} and Shaoli Deng and Yuqing Cheng and Masaki Magari and Haberman, {Ann M.}",

note = "Funding Information: We thank Dr. Aaron J Marshall for critical review of the manuscript and Dr. K Mark Ansel for kindly providing the YFP-BCL6 knock-in reporter mice with permission from Dr. Takahura Okada. This work was supported by NIH R01AI080850 and R21AI101704 grants to AMH, and TTZ was supported by a Canadian Institute of Health Research Postdoctoral Fellowship. Publisher Copyright: {\textcopyright} Zhang et al.",

year = "2017",

month = may,

day = "12",

doi = "10.7554/eLife.19552",

language = "English",

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T1 - Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

AU - Zhang, Ting Ting

AU - Gonzalez, David G.

AU - Cote, Christine M.

AU - Kerfoot, Steven M.

AU - Deng, Shaoli

AU - Cheng, Yuqing

AU - Magari, Masaki

AU - Haberman, Ann M.

N1 - Funding Information: We thank Dr. Aaron J Marshall for critical review of the manuscript and Dr. K Mark Ansel for kindly providing the YFP-BCL6 knock-in reporter mice with permission from Dr. Takahura Okada. This work was supported by NIH R01AI080850 and R21AI101704 grants to AMH, and TTZ was supported by a Canadian Institute of Health Research Postdoctoral Fellowship. Publisher Copyright: © Zhang et al.

PY - 2017/5/12

Y1 - 2017/5/12

N2 - To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.

AB - To reconcile conflicting reports on the role of CD40 signaling in germinal center (GC) formation, we examined the earliest stages of murine GC B cell differentiation. Peri-follicular GC precursors first expressed intermediate levels of BCL6 while co-expressing the transcription factors RelB and IRF4, the latter known to repress Bcl6 transcription. Transition of GC precursors to the BCL6hi follicular state was associated with cell division, although the number of required cell divisions was immunogen dose dependent. Potentiating T cell help or CD40 signaling in these GC precursors actively repressed GC B cell maturation and diverted their fate towards plasmablast differentiation, whereas depletion of CD4+ T cells promoted this initial transition. Thus while CD40 signaling in B cells is necessary to generate the immediate precursors of GC B cells, transition to the BCL6hi follicular state is promoted by a regional and transient diminution of T cell help.

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Germinal center B cell development has distinctly regulated stages completed by disengagement from T cell help

Abstract

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