Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation

B cells responding to T-dependent antigen either differentiate rapidly into extrafollicular plasma cells or enter germinal centers and undergo somatic hypermutation and affinity maturation. However, the physiological cues that direct B cell differentiation down one pathway versus the other are unkno...

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Main Authors:	Paus, Didrik, Phan, Tri Giang, Chan, Tyani D., Gardam, Sandra, Basten, Antony, Brink, Robert
Format:	Online
Language:	English
Published:	The Rockefeller University Press 2006
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118299/

id	pubmed-2118299
recordtype	oai_dc
spelling	pubmed-21182992007-12-13 Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation Paus, Didrik Phan, Tri Giang Chan, Tyani D. Gardam, Sandra Basten, Antony Brink, Robert Articles B cells responding to T-dependent antigen either differentiate rapidly into extrafollicular plasma cells or enter germinal centers and undergo somatic hypermutation and affinity maturation. However, the physiological cues that direct B cell differentiation down one pathway versus the other are unknown. Here we show that the strength of the initial interaction between B cell receptor (BCR) and antigen is a primary determinant of this decision. B cells expressing a defined BCR specificity for hen egg lysozyme (HEL) were challenged with sheep red blood cell conjugates of a series of recombinant mutant HEL proteins engineered to bind this BCR over a 10,000-fold affinity range. Decreasing either initial BCR affinity or antigen density was found to selectively remove the extrafollicular plasma cell response but leave the germinal center response intact. Moreover, analysis of competing B cells revealed that high affinity specificities are more prevalent in the extrafollicular plasma cell versus the germinal center B cell response. Thus, the effectiveness of early T-dependent antibody responses is optimized by preferentially steering B cells reactive against either high affinity or abundant epitopes toward extrafollicular plasma cell differentiation. Conversely, responding clones with weaker antigen reactivity are primarily directed to germinal centers where they undergo affinity maturation. The Rockefeller University Press 2006-04-17 /pmc/articles/PMC2118299/ /pubmed/16606676 http://dx.doi.org/10.1084/jem.20060087 Text en Copyright © 2006, The Rockefeller University Press 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 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Paus, Didrik Phan, Tri Giang Chan, Tyani D. Gardam, Sandra Basten, Antony Brink, Robert
spellingShingle	Paus, Didrik Phan, Tri Giang Chan, Tyani D. Gardam, Sandra Basten, Antony Brink, Robert Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation
author_facet	Paus, Didrik Phan, Tri Giang Chan, Tyani D. Gardam, Sandra Basten, Antony Brink, Robert
author_sort	Paus, Didrik
title	Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation
title_short	Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation
title_full	Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation
title_fullStr	Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation
title_full_unstemmed	Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation
title_sort	antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center b cell differentiation
description	B cells responding to T-dependent antigen either differentiate rapidly into extrafollicular plasma cells or enter germinal centers and undergo somatic hypermutation and affinity maturation. However, the physiological cues that direct B cell differentiation down one pathway versus the other are unknown. Here we show that the strength of the initial interaction between B cell receptor (BCR) and antigen is a primary determinant of this decision. B cells expressing a defined BCR specificity for hen egg lysozyme (HEL) were challenged with sheep red blood cell conjugates of a series of recombinant mutant HEL proteins engineered to bind this BCR over a 10,000-fold affinity range. Decreasing either initial BCR affinity or antigen density was found to selectively remove the extrafollicular plasma cell response but leave the germinal center response intact. Moreover, analysis of competing B cells revealed that high affinity specificities are more prevalent in the extrafollicular plasma cell versus the germinal center B cell response. Thus, the effectiveness of early T-dependent antibody responses is optimized by preferentially steering B cells reactive against either high affinity or abundant epitopes toward extrafollicular plasma cell differentiation. Conversely, responding clones with weaker antigen reactivity are primarily directed to germinal centers where they undergo affinity maturation.
publisher	The Rockefeller University Press
publishDate	2006
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2118299/
_version_	1611414677277900800

Antigen recognition strength regulates the choice between extrafollicular plasma cell and germinal center B cell differentiation

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