Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular Zone

Steven M. Kerfoot; Gur Yaari; Jaymin R. Patel; Kody L. Johnson; David G. Gonzalez; Steven H. Kleinstein; Ann M. Haberman

doi:10.1016/j.immuni.2011.03.024

Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular Zone

Steven M. Kerfoot, Gur Yaari, Jaymin R. Patel, Kody L. Johnson, David G. Gonzalez, Steven H. Kleinstein, Ann M. Haberman

Yale University

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

378 Scopus citations

Abstract

We identify the interfollicular (IF) zone as the site where germinal center B cell and T follicular helper (Tfh) cell differentiation initiates. For the first 2 days postimmunization, antigen-specific T and B cells remained confined within the IF zone, formed long-lived interactions, and upregulated the transcriptional repressor Bcl6. T cells also acquired the Tfh cell markers CXCR5, PD-1, and GL7. Responding B and T cells migrated to the follicle interior directly from the IF zone, T cell immigration preceding B cells by 1 day. Notably, in the absence of cognate B cells, Tfh cells still formed and migrated to the follicle. However, without such B cells, PD-1, ICOS, and GL7 were no longer expressed on follicular Bcl6^hi T cells that nevertheless persisted in the follicle. Thus, Ag-specific B cells are required for the maintenance of the PD-1^hiICOS^hiGL7^hi Tfh cell phenotype within the follicle, but not for their initial differentiation in the IF zone.

Original language	English
Pages (from-to)	947-960
Number of pages	14
Journal	Immunity
Volume	34
Issue number	6
DOIs	https://doi.org/10.1016/j.immuni.2011.03.024
State	Published - 24 Jun 2011
Externally published	Yes

Bibliographical note

Funding Information:
The authors would like to thank K. Good-Jacobson and A. Poholek for their constructive discussion and A. Hauser for her assistance in establishing the multiphoton facility. We thank M. Shlomchik for thoughtful input and critical reading of the manuscript. The excellent husbandry of A. Durso and the technicians of the Yale Animal Resources Center is also appreciated. This work was supported by National Institutes of Health grants R01AI080850 and P30AR053495. S.M.K. was supported by a fellowship from the Canadian Institutes of Health Research and the Gershon/Trudeau Fellowship, and is the current recipient of the Garrett Herman endMS Research and Training Network Career Development Award from the Multiple Sclerosis Society of Canada.

Funding

The authors would like to thank K. Good-Jacobson and A. Poholek for their constructive discussion and A. Hauser for her assistance in establishing the multiphoton facility. We thank M. Shlomchik for thoughtful input and critical reading of the manuscript. The excellent husbandry of A. Durso and the technicians of the Yale Animal Resources Center is also appreciated. This work was supported by National Institutes of Health grants R01AI080850 and P30AR053495. S.M.K. was supported by a fellowship from the Canadian Institutes of Health Research and the Gershon/Trudeau Fellowship, and is the current recipient of the Garrett Herman endMS Research and Training Network Career Development Award from the Multiple Sclerosis Society of Canada.

Funders	Funder number
National Institutes of Health	R01AI080850
National Institute of Arthritis and Musculoskeletal and Skin Diseases	P30AR053495
Canadian Institutes of Health Research
Multiple Sclerosis Society of Canada

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.immuni.2011.03.024

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title = "Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular Zone",

abstract = "We identify the interfollicular (IF) zone as the site where germinal center B cell and T follicular helper (Tfh) cell differentiation initiates. For the first 2 days postimmunization, antigen-specific T and B cells remained confined within the IF zone, formed long-lived interactions, and upregulated the transcriptional repressor Bcl6. T cells also acquired the Tfh cell markers CXCR5, PD-1, and GL7. Responding B and T cells migrated to the follicle interior directly from the IF zone, T cell immigration preceding B cells by 1 day. Notably, in the absence of cognate B cells, Tfh cells still formed and migrated to the follicle. However, without such B cells, PD-1, ICOS, and GL7 were no longer expressed on follicular Bcl6hi T cells that nevertheless persisted in the follicle. Thus, Ag-specific B cells are required for the maintenance of the PD-1hiICOShiGL7hi Tfh cell phenotype within the follicle, but not for their initial differentiation in the IF zone.",

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N2 - We identify the interfollicular (IF) zone as the site where germinal center B cell and T follicular helper (Tfh) cell differentiation initiates. For the first 2 days postimmunization, antigen-specific T and B cells remained confined within the IF zone, formed long-lived interactions, and upregulated the transcriptional repressor Bcl6. T cells also acquired the Tfh cell markers CXCR5, PD-1, and GL7. Responding B and T cells migrated to the follicle interior directly from the IF zone, T cell immigration preceding B cells by 1 day. Notably, in the absence of cognate B cells, Tfh cells still formed and migrated to the follicle. However, without such B cells, PD-1, ICOS, and GL7 were no longer expressed on follicular Bcl6hi T cells that nevertheless persisted in the follicle. Thus, Ag-specific B cells are required for the maintenance of the PD-1hiICOShiGL7hi Tfh cell phenotype within the follicle, but not for their initial differentiation in the IF zone.

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Germinal Center B Cell and T Follicular Helper Cell Development Initiates in the Interfollicular Zone

Abstract

Bibliographical note

Funding

UN SDGs

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