Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts.

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Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts. / Marshall, Jennifer; Zhang, Yang; Pallan, Lalit; Hsu, MC; Khan, Mahmood; Cunningham, AC; MacLennan, Ian; Toellner, Kai-Michael.

In: European Journal of Immunology, Vol. 41, No. 12, 01.12.2011, p. 3506-12.

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@article{e2bea4b0e12c4adaacc0ffd70286832e,
title = "Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts.",
abstract = "Rapid production of neutralizing antibody can be critical for limiting the spread of infection. Such early antibody results when B blasts mature directly to plasmablasts without forming germinal centres. These extrafollicular responses can involve Ig class switch recombination (CSR), producing antibody that can readily disseminate through infected tissues. The present study identifies the differentiation stage where CSR occurs in an extrafollicular response induced by 4-hydroxy-3-nitrophenyl acetyl (NP) conjugated to Ficoll (NP-Ficoll). To do this we took advantage of the antigen dose dependency of CSR in this response. Thus, while both 30 mg and 1 mg NP-Ficoll induces plasmablasts, only the higher antigen dose induces CSR. Activation-induced cytidine deaminase (AID) is critical for CSR and in keeping with this a proportion of NP-specific B blasts induced by 30 mg NP-Ficoll express AID. None of the B blasts responding to the non-CSR-inducing 1 mg dose of NP-Ficoll express AID. We confirmed that CSR occurs in B blasts by demonstrating the presence of rearranged heavy chain transcripts in B blasts in the 30 mg response. CSR in this extrafollicular response is confined to B blasts, because NP-specific plasmablasts, identified by expressing CD138 and Blimp1, no longer express AID and cannot undergo CSR.",
keywords = "Antibodies, B cells, cell differentiation, spleen",
author = "Jennifer Marshall and Yang Zhang and Lalit Pallan and MC Hsu and Mahmood Khan and AC Cunningham and Ian MacLennan and Kai-Michael Toellner",
year = "2011",
month = dec,
day = "1",
doi = "10.1002/eji.201141762",
language = "English",
volume = "41",
pages = "3506--12",
journal = "European Journal of Immunology",
issn = "0014-2980",
publisher = "Wiley-VCH Verlag",
number = "12",

}

RIS

TY - JOUR

T1 - Early B blasts acquire a capacity for Ig class switch recombination that is lost as they become plasmablasts.

AU - Marshall, Jennifer

AU - Zhang, Yang

AU - Pallan, Lalit

AU - Hsu, MC

AU - Khan, Mahmood

AU - Cunningham, AC

AU - MacLennan, Ian

AU - Toellner, Kai-Michael

PY - 2011/12/1

Y1 - 2011/12/1

N2 - Rapid production of neutralizing antibody can be critical for limiting the spread of infection. Such early antibody results when B blasts mature directly to plasmablasts without forming germinal centres. These extrafollicular responses can involve Ig class switch recombination (CSR), producing antibody that can readily disseminate through infected tissues. The present study identifies the differentiation stage where CSR occurs in an extrafollicular response induced by 4-hydroxy-3-nitrophenyl acetyl (NP) conjugated to Ficoll (NP-Ficoll). To do this we took advantage of the antigen dose dependency of CSR in this response. Thus, while both 30 mg and 1 mg NP-Ficoll induces plasmablasts, only the higher antigen dose induces CSR. Activation-induced cytidine deaminase (AID) is critical for CSR and in keeping with this a proportion of NP-specific B blasts induced by 30 mg NP-Ficoll express AID. None of the B blasts responding to the non-CSR-inducing 1 mg dose of NP-Ficoll express AID. We confirmed that CSR occurs in B blasts by demonstrating the presence of rearranged heavy chain transcripts in B blasts in the 30 mg response. CSR in this extrafollicular response is confined to B blasts, because NP-specific plasmablasts, identified by expressing CD138 and Blimp1, no longer express AID and cannot undergo CSR.

AB - Rapid production of neutralizing antibody can be critical for limiting the spread of infection. Such early antibody results when B blasts mature directly to plasmablasts without forming germinal centres. These extrafollicular responses can involve Ig class switch recombination (CSR), producing antibody that can readily disseminate through infected tissues. The present study identifies the differentiation stage where CSR occurs in an extrafollicular response induced by 4-hydroxy-3-nitrophenyl acetyl (NP) conjugated to Ficoll (NP-Ficoll). To do this we took advantage of the antigen dose dependency of CSR in this response. Thus, while both 30 mg and 1 mg NP-Ficoll induces plasmablasts, only the higher antigen dose induces CSR. Activation-induced cytidine deaminase (AID) is critical for CSR and in keeping with this a proportion of NP-specific B blasts induced by 30 mg NP-Ficoll express AID. None of the B blasts responding to the non-CSR-inducing 1 mg dose of NP-Ficoll express AID. We confirmed that CSR occurs in B blasts by demonstrating the presence of rearranged heavy chain transcripts in B blasts in the 30 mg response. CSR in this extrafollicular response is confined to B blasts, because NP-specific plasmablasts, identified by expressing CD138 and Blimp1, no longer express AID and cannot undergo CSR.

KW - Antibodies

KW - B cells

KW - cell differentiation

KW - spleen

U2 - 10.1002/eji.201141762

DO - 10.1002/eji.201141762

M3 - Article

C2 - 21932446

VL - 41

SP - 3506

EP - 3512

JO - European Journal of Immunology

JF - European Journal of Immunology

SN - 0014-2980

IS - 12

ER -