Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

S1PR2 and CXCR5 cooperatively regulate localization of Tfh cells in GCs to support GC responses.

Abstract

Follicular helper T (Tfh) cells access the B cell follicle to promote antibody responses and are particularly important for germinal center (GC) reactions. However, the molecular mechanisms of how Tfh cells are physically associated with GCs are incompletely understood. We report that the sphingosine-1-phosphate receptor 2 (S1PR2) gene is highly expressed in a subpopulation of Tfh cells that localizes in GCs. S1PR2-deficient Tfh cells exhibited reduced accumulation in GCs due to their impaired retention. T cells deficient in both S1PR2 and CXCR5 were ineffective in supporting GC responses compared with T cells deficient only in CXCR5. These results suggest that S1PR2 and CXCR5 cooperatively regulate localization of Tfh cells in GCs to support GC responses.

Related collections

Most cited references 16

Record: found
Abstract: found
Article: not found

Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1.

Mehrdad Matloubian, Charles G. Lo, Guy Cinamon … (2004)

Adaptive immunity depends on T-cell exit from the thymus and T and B cells travelling between secondary lymphoid organs to survey for antigens. After activation in lymphoid organs, T cells must again return to circulation to reach sites of infection; however, the mechanisms regulating lymphoid organ exit are unknown. An immunosuppressant drug, FTY720, inhibits lymphocyte emigration from lymphoid organs, and phosphorylated FTY720 binds and activates four of the five known sphingosine-1-phosphate (S1P) receptors. However, the role of S1P receptors in normal immune cell trafficking is unclear. Here we show that in mice whose haematopoietic cells lack a single S1P receptor (S1P1; also known as Edg1) there are no T cells in the periphery because mature T cells are unable to exit the thymus. Although B cells are present in peripheral lymphoid organs, they are severely deficient in blood and lymph. Adoptive cell transfer experiments establish an intrinsic requirement for S1P1 in T and B cells for lymphoid organ egress. Furthermore, S1P1-dependent chemotactic responsiveness is strongly upregulated in T-cell development before exit from the thymus, whereas S1P1 is downregulated during peripheral lymphocyte activation, and this is associated with retention in lymphoid organs. We find that FTY720 treatment downregulates S1P1, creating a temporary pharmacological S1P1-null state in lymphocytes, providing an explanation for the mechanism of FTY720-induced lymphocyte sequestration. These findings establish that S1P1 is essential for lymphocyte recirculation and that it regulates egress from both thymus and peripheral lymphoid organs.

0 comments Cited 671 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells

Kim L. Good-Jacobson, Courtney Szumilas, Lieping Chen … (2010)

Memory B and plasma cells (PCs) are generated in the germinal center (GC). As PD-1 is highly expressed in T follicular helper cells (TFH), we investigated the role of PD-1 signaling in the humoral response. We found that PD-L1 and PD-L2 are upregulated on GC B cells. Pdcd1lg2 −/− , CD274 −/− Pdcd1lg2 −/− and Pdcd1 −/− mice had reduced numbers of long-lived PCs. The mechanism involved increased GC cell death and decreased TFH cytokine production in the absence of PD-1; the effect was selective, as remaining PCs had higher affinity. PD-1 expression on T cells and PD-L2 expression on B cells controlled TFH and PC numbers. Thus, PD-1 regulates selection and survival in the GC, impacting the quantity and quality of long-lived PCs.

0 comments Cited 234 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages.

P Mombaerts, A R Clarke, M Rudnicki … (1992)

Analysis of mice carrying mutant T-cell antigen receptor (TCR) genes indicates that TCR-beta gene rearrangement or expression is critical for the differentiation of CD4-CD8- thymocytes to CD4+CD8+ thymocytes, as well as for the expansion of the pool of CD4+CD8+ cells. TCR-alpha is irrelevant in these developmental processes. The development of gamma delta T cells does not depend on either TCR-alpha or TCR-beta.

0 comments Cited 182 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Journal

Journal ID (nlm-ta): J Exp Med

Journal ID (iso-abbrev): J. Exp. Med

Journal ID (hwp): jem

Journal ID (publisher-id): jem

Title: The Journal of Experimental Medicine

Publisher: The Rockefeller University Press

ISSN (Print): 0022-1007

ISSN (Electronic): 1540-9538

Publication date (Print): 30 June 2014

Volume: 211

Issue: 7

Pages: 1297-1305

Affiliations

[1 ]Laboratory for Tissue Dynamics , [2 ]Laboratory for Lymphocyte Differentiation , [3 ]Laboratory for Immune Homeostasis , and [4 ]Laboratory for Cytokine Regulation, RCAI, RIKEN Center for Integrative Medical Sciences (IMS-RCAI), Yokohama, Kanagawa 230-0045, Japan

[5 ]Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka 565-0871, Japan

[6 ]Department of Microbiology and Immunology and [7 ]Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94143

[8 ]Division of Molecular Pathology, Research Institute for Biomedical Science, Tokyo University of Science, Noda, Chiba 278-0022, Japan

[9 ]PRESTO, Japan Science and Technology Agency, Saitama, Saitama 332-0012, Japan

[10 ]Graduate School of Medical Life Science, Yokohama City University, Yokohama 230-0045, Japan

Author notes

CORRESPONDENCE Takaharu Okada: tokada@ 123456rcai.riken.jp

Article

Publisher ID: 20131666

DOI: 10.1084/jem.20131666

PMC ID: 4076581

PubMed ID: 24913235

SO-VID: 7b1dd2bd-153d-4f8c-a1af-e98c1c4ef0a8

License:

This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 3.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/3.0/).

Sphingosine-1-phosphate receptor 2 is critical for follicular helper T cell retention in germinal centers

Read this article at

Abstract

Abstract

Related collections

Gamma Delta T cells

Most cited references 16

Lymphocyte egress from thymus and peripheral lymphoid organs is dependent on S1P receptor 1.

PD-1 regulates germinal center B cell survival and the formation and affinity of long-lived plasma cells

Mutations in T-cell antigen receptor genes alpha and beta block thymocyte development at different stages.

Author and article information

Journal

Affiliations

Author notes

Article

History

Categories

Comments

Comment on this article

Similar content 38

Cited by 56

Most referenced authors 240