Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation

Radhika Goenka; Andrew H. Matthews; Bochao Zhang; Patrick J. O'Neill; Jean L. Scholz; Thi Sau Migone; Warren J. Leonard; William Stohl; Uri Hershberg; Michael P. Cancro

doi:10.1084/jem.20130505

Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation

Radhika Goenka, Andrew H. Matthews, Bochao Zhang, Patrick J. O'Neill, Jean L. Scholz, Thi Sau Migone, Warren J. Leonard, William Stohl, Uri Hershberg, Michael P. Cancro

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

Abstract

We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reaction and affinity maturation. Despite ample BLyS retention on B cells in follicular (FO) regions, the GC microenvironment lacks substantial BLyS. This reflects IL-21-mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) on GC B cells, thus limiting their capacity for BLyS binding and retention. Within the GC, FO helper T cells (T_FH cells) provide a local source of BLyS. Whereas T cell-derived BLyS is dispensable for normal GC cellularity and somatic hypermutation, it is required for the efficient selection of high affinity GC B cell clones. These findings suggest that during affinity maturation, high affinity clones rely on T_FH-derived BLyS for their persistence.

Original language	English
Pages (from-to)	45-56
Number of pages	12
Journal	Journal of Experimental Medicine
Volume	211
Issue number	1
DOIs	https://doi.org/10.1084/jem.20130505
State	Published - Jan 2014
Externally published	Yes

ASJC Scopus subject areas

Immunology and Allergy
Immunology

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10.1084/jem.20130505

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title = "Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation",

abstract = "We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reaction and affinity maturation. Despite ample BLyS retention on B cells in follicular (FO) regions, the GC microenvironment lacks substantial BLyS. This reflects IL-21-mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) on GC B cells, thus limiting their capacity for BLyS binding and retention. Within the GC, FO helper T cells (TFH cells) provide a local source of BLyS. Whereas T cell-derived BLyS is dispensable for normal GC cellularity and somatic hypermutation, it is required for the efficient selection of high affinity GC B cell clones. These findings suggest that during affinity maturation, high affinity clones rely on TFH-derived BLyS for their persistence.",

author = "Radhika Goenka and Matthews, {Andrew H.} and Bochao Zhang and O'Neill, {Patrick J.} and Scholz, {Jean L.} and Migone, {Thi Sau} and Leonard, {Warren J.} and William Stohl and Uri Hershberg and Cancro, {Michael P.}",

year = "2014",

month = jan,

doi = "10.1084/jem.20130505",

language = "English",

volume = "211",

pages = "45--56",

journal = "Journal of Experimental Medicine",

issn = "0022-1007",

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T1 - Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation

AU - Goenka, Radhika

AU - Matthews, Andrew H.

AU - Zhang, Bochao

AU - O'Neill, Patrick J.

AU - Scholz, Jean L.

AU - Migone, Thi Sau

AU - Leonard, Warren J.

AU - Stohl, William

AU - Hershberg, Uri

AU - Cancro, Michael P.

PY - 2014/1

Y1 - 2014/1

N2 - We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reaction and affinity maturation. Despite ample BLyS retention on B cells in follicular (FO) regions, the GC microenvironment lacks substantial BLyS. This reflects IL-21-mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) on GC B cells, thus limiting their capacity for BLyS binding and retention. Within the GC, FO helper T cells (TFH cells) provide a local source of BLyS. Whereas T cell-derived BLyS is dispensable for normal GC cellularity and somatic hypermutation, it is required for the efficient selection of high affinity GC B cell clones. These findings suggest that during affinity maturation, high affinity clones rely on TFH-derived BLyS for their persistence.

AB - We have assessed the role of B lymphocyte stimulator (BLyS) and its receptors in the germinal center (GC) reaction and affinity maturation. Despite ample BLyS retention on B cells in follicular (FO) regions, the GC microenvironment lacks substantial BLyS. This reflects IL-21-mediated down-regulation of the BLyS receptor TACI (transmembrane activator and calcium modulator and cyclophilin ligand interactor) on GC B cells, thus limiting their capacity for BLyS binding and retention. Within the GC, FO helper T cells (TFH cells) provide a local source of BLyS. Whereas T cell-derived BLyS is dispensable for normal GC cellularity and somatic hypermutation, it is required for the efficient selection of high affinity GC B cell clones. These findings suggest that during affinity maturation, high affinity clones rely on TFH-derived BLyS for their persistence.

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EP - 56

JO - Journal of Experimental Medicine

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ER -

Local BLyS production by T follicular cells mediates retention of high affinity B cells during affinity maturation

Abstract

ASJC Scopus subject areas

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