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-cell blasts mature directly to plasmablasts without forming germinal centers. 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 and 1 μg NP-Ficoll induce plasmablasts, only the higher antigen dose induces CSR. Activation-induce cytidine deaminase (AID) is critical for CSR and in keeping with this a proportion of NP-specific B-cell blasts induced by 30 μg NP-Ficoll express AID. None of the B blasts responding to the non-CSR-inducing 1 μg 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 μg response. CSR in this extrafollicular response is confined to B blasts, because NP-specific plasmablasts, identified by expressing CD138 and Blimp-1, no longer express AID and cannot undergo CSR.
authors.affiliation: MRC Centre for Immune Regulation, School of Immunity and Infection, University of Birmingham, Birmingham, UK.
authors.forename: Jennifer L
authors.initials: JL
authors.lastname: Marshall
authors.forename: Yang
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lalit
authors.initials: L
authors.lastname: Pallan
authors.forename: Mei-Chi
authors.initials: MC
authors.lastname: Hsu
authors.forename: Mahmood
authors.initials: M
authors.lastname: Khan
authors.forename: Adam F
authors.initials: AF
authors.lastname: Cunningham
authors.forename: Ian C M
authors.initials: IC
authors.lastname: MacLennan
authors.forename: Kai-Michael
authors.initials: KM
authors.lastname: Toellner
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000276:immunology* / Q000378:metabolism*; D003564:Cytidine Deaminase / Q000235:genetics / Q000276:immunology; D005362:Ficoll / Q000494:pharmacology; D018796:Immunoconjugates / Q000276:immunology; D017578:Immunoglobulin Class Switching / Q000235:genetics* / Q000276:immunology*; D007143:Immunoglobulin Heavy Chains / Q000235:genetics / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D009596:Nitrophenols / Q000494:pharmacology; D010648:Phenylacetates / Q000494:pharmacology; D010950:Plasma Cells / Q000276:immunology*; D000074462:Positive Regulatory Domain I-Binding Factor 1; D053668:Syndecan-1 / Q000235:genetics / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics / Q000276:immunology
chemical_list: D018796:Immunoconjugates; D007143:Immunoglobulin Heavy Chains; D009596:Nitrophenols; D010648:Phenylacetates; C513258:Prdm1 protein, mouse; D053668:Syndecan-1; D014157:Transcription Factors; C026242:4-hydroxy-5-nitrophenyl acetic acid; D005362:Ficoll; D000074462:Positive Regulatory Domain I-Binding Factor 1; D003564:Cytidine Deaminase