Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

Hu Yan; Longyan Wu; Changming Shih; Shiyue Hou; Jingwen Shi; Tianyang Mao; Wenbin Chen; Bhavani Melvin; Robert J. Rigby; Yingjia Chen; Haochen Jiang; Roland H. Friedel; Carola G. Vinuesa; Hai Qi

doi:10.1016/j.celrep.2017.04.022

Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

Hu Yan, Longyan Wu, Changming Shih, Shiyue Hou, Jingwen Shi, Tianyang Mao, Wenbin Chen, Bhavani Melvin, Robert J. Rigby, Yingjia Chen, Haochen Jiang, Roland H. Friedel, Carola G. Vinuesa, Hai Qi^*

^*Corresponding author for this work

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

38 Citations (Scopus)

Abstract

Follicular T helper (T_FH) cells orchestrate the germinal center (GC) response locally. T_FH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for T_FH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on T_FH cells. Sema4C on T_FH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases T_FH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from T_FH cells causes T_FH accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC T_FH recruitment and function and optimize antibody responses.

Original language	English
Pages (from-to)	995-1007
Number of pages	13
Journal	Cell Reports
Volume	19
Issue number	5
DOIs	https://doi.org/10.1016/j.celrep.2017.04.022
Publication status	Published - 2 May 2017

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@article{679283abcd724fd09b7f28b6855a437c,

title = "Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center",

abstract = "Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells. Sema4C on TFH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases TFH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC TFH recruitment and function and optimize antibody responses.",

keywords = "Plexin B2, Semaphorin 4C, Semaphorin 4D, cell adhesion, cell migration, follicular T-helper cells, germinal center, humoral immunity, intravital imaging, plasma cells",

author = "Hu Yan and Longyan Wu and Changming Shih and Shiyue Hou and Jingwen Shi and Tianyang Mao and Wenbin Chen and Bhavani Melvin and Rigby, {Robert J.} and Yingjia Chen and Haochen Jiang and Friedel, {Roland H.} and Vinuesa, {Carola G.} and Hai Qi",

note = "Publisher Copyright: {\textcopyright} 2017 The Author(s)",

year = "2017",

month = may,

day = "2",

doi = "10.1016/j.celrep.2017.04.022",

language = "English",

volume = "19",

pages = "995--1007",

journal = "Cell Reports",

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publisher = "Elsevier B.V.",

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TY - JOUR

T1 - Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

AU - Yan, Hu

AU - Wu, Longyan

AU - Shih, Changming

AU - Hou, Shiyue

AU - Shi, Jingwen

AU - Mao, Tianyang

AU - Chen, Wenbin

AU - Melvin, Bhavani

AU - Rigby, Robert J.

AU - Chen, Yingjia

AU - Jiang, Haochen

AU - Friedel, Roland H.

AU - Vinuesa, Carola G.

AU - Qi, Hai

PY - 2017/5/2

Y1 - 2017/5/2

N2 - Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells. Sema4C on TFH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases TFH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC TFH recruitment and function and optimize antibody responses.

AB - Follicular T helper (TFH) cells orchestrate the germinal center (GC) response locally. TFH localization in GCs is controlled by chemo-guidance cues and antigen-specific adhesion. Here. we define an antigen-independent, contact-dependent, adhesive guidance system for TFH cells. Unusual for amoeboid cell migration, the system is composed of transmembrane plexin B2 (PlxnB2) molecule, which is highly expressed by GC B cells, and its transmembrane binding partner semaphorin 4C (Sema4C), which is upregulated on TFH cells. Sema4C on TFH cells serves as a receptor to sense the GC-presented PlxnB2 cue and biases TFH migration inwards at the GC edge to promote GC access. The absence of PlxnB2 from the GC or Sema4C from TFH cells causes TFH accumulation along the GC border, impairs T-B cell interactions in the GC, and is associated with defective plasma cell production and affinity maturation. Therefore, Sema4C and PlxnB2 regulate GC TFH recruitment and function and optimize antibody responses.

KW - Plexin B2

KW - Semaphorin 4C

KW - Semaphorin 4D

KW - cell adhesion

KW - cell migration

KW - follicular T-helper cells

KW - germinal center

KW - humoral immunity

KW - intravital imaging

KW - plasma cells

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U2 - 10.1016/j.celrep.2017.04.022

DO - 10.1016/j.celrep.2017.04.022

M3 - Article

SN - 2211-1247

VL - 19

SP - 995

EP - 1007

JO - Cell Reports

JF - Cell Reports

IS - 5

ER -

Plexin B2 and Semaphorin 4C Guide T Cell Recruitment and Function in the Germinal Center

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