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Aiolos is required for the generation of high affinity bone marrow plasma cells responsible for long-term immunity.

Cortés M, Georgopoulos K - J. Exp. Med. (2004)

Bottom Line: Lack of Aiolos does not alter expression of any of the previously described factors required for general plasma cell differentiation.No defect in somatic hypermutation, the generation of memory B cells, or short-lived high affinity plasma cells in the spleen was observed upon rechallenge.These studies support a model by which the high affinity plasma cell population in the BM undergoes a unique differentiation program that is dependent on Aiolos.

View Article: PubMed Central - PubMed

Affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

ABSTRACT
Antigenic encounter generates long-term immunity sustained by long-lived high affinity plasma cells resident in the bone marrow (BM). Here we show that the Ikaros family member, Aiolos, is specifically required for the generation of these plasma cells. Failure to generate high affinity plasma cells in the BM and to sustain serum antibody titers is apparent after both primary and secondary immunization of Aiolos(-)(/)(-) mice with a range of hapten concentrations. Chimera reconstitutions demonstrate that the BM plasma cell defect is B cell intrinsic. Lack of Aiolos does not alter expression of any of the previously described factors required for general plasma cell differentiation. No defect in somatic hypermutation, the generation of memory B cells, or short-lived high affinity plasma cells in the spleen was observed upon rechallenge. These studies support a model by which the high affinity plasma cell population in the BM undergoes a unique differentiation program that is dependent on Aiolos.

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Impaired production of high affinity AFCs in Aio−/− mice after primary immunization. (A) Frequencies of NP-specific IgM-producing AFCs in the spleen (left) and BM (right) of WT (open bars) and Aio−/− (solid bars) at 14 and 30 d after primary immunization. IgG1-producing AFCs in the BM (B) and spleen (C) of WT (○) and Aio−/− (•) mice were measured at 14, 30, 40, and 120 d after primary immunization. Data were obtained from ELISPOT assays using NP4 and NP23 as the coating Ags. High affinity AFCs by NP4 binding and total anti-NP AFCs were measured by NP23 binding. Each point represents an individual mouse and results represent one experiment of at least three with similar findings. Horizontal bars in B and C indicate the average number of AFCs at each time point.
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fig1: Impaired production of high affinity AFCs in Aio−/− mice after primary immunization. (A) Frequencies of NP-specific IgM-producing AFCs in the spleen (left) and BM (right) of WT (open bars) and Aio−/− (solid bars) at 14 and 30 d after primary immunization. IgG1-producing AFCs in the BM (B) and spleen (C) of WT (○) and Aio−/− (•) mice were measured at 14, 30, 40, and 120 d after primary immunization. Data were obtained from ELISPOT assays using NP4 and NP23 as the coating Ags. High affinity AFCs by NP4 binding and total anti-NP AFCs were measured by NP23 binding. Each point represents an individual mouse and results represent one experiment of at least three with similar findings. Horizontal bars in B and C indicate the average number of AFCs at each time point.

Mentions: To determine the role of Aiolos during an immune response, Aio−/− mice were immunized with the T cell–dependent Ag NP-CGG in alum. The Aio−/− mice used in this study were 3–5 wk of age, a time point before the “spontaneous” development of GC reactions, which form over time in the absence of immunization (12). The ligands NP4-BSA or NP23-BSA were used to determine the affinity of Abs produced by AFC in an ELISPOT assay. Densely haptenated NP (NP23-BSA)–coated plates are bound by both high and low affinity anti-NP Abs, whereas sparsely haptenated BSA (NP4-BSA)–coated plates are bound only by high affinity anti-NP Abs. Low affinity IgM-producing AFCs in the spleen and BM of Aio−/− mice were within physiological range at 14 d after immunization and declined by day 30 to levels similar to WT (Fig. 1 A). Thus, Aio−/− mice showed no defect in the production of low affinity AFCs during the primary response.


Aiolos is required for the generation of high affinity bone marrow plasma cells responsible for long-term immunity.

Cortés M, Georgopoulos K - J. Exp. Med. (2004)

Impaired production of high affinity AFCs in Aio−/− mice after primary immunization. (A) Frequencies of NP-specific IgM-producing AFCs in the spleen (left) and BM (right) of WT (open bars) and Aio−/− (solid bars) at 14 and 30 d after primary immunization. IgG1-producing AFCs in the BM (B) and spleen (C) of WT (○) and Aio−/− (•) mice were measured at 14, 30, 40, and 120 d after primary immunization. Data were obtained from ELISPOT assays using NP4 and NP23 as the coating Ags. High affinity AFCs by NP4 binding and total anti-NP AFCs were measured by NP23 binding. Each point represents an individual mouse and results represent one experiment of at least three with similar findings. Horizontal bars in B and C indicate the average number of AFCs at each time point.
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Related In: Results  -  Collection

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fig1: Impaired production of high affinity AFCs in Aio−/− mice after primary immunization. (A) Frequencies of NP-specific IgM-producing AFCs in the spleen (left) and BM (right) of WT (open bars) and Aio−/− (solid bars) at 14 and 30 d after primary immunization. IgG1-producing AFCs in the BM (B) and spleen (C) of WT (○) and Aio−/− (•) mice were measured at 14, 30, 40, and 120 d after primary immunization. Data were obtained from ELISPOT assays using NP4 and NP23 as the coating Ags. High affinity AFCs by NP4 binding and total anti-NP AFCs were measured by NP23 binding. Each point represents an individual mouse and results represent one experiment of at least three with similar findings. Horizontal bars in B and C indicate the average number of AFCs at each time point.
Mentions: To determine the role of Aiolos during an immune response, Aio−/− mice were immunized with the T cell–dependent Ag NP-CGG in alum. The Aio−/− mice used in this study were 3–5 wk of age, a time point before the “spontaneous” development of GC reactions, which form over time in the absence of immunization (12). The ligands NP4-BSA or NP23-BSA were used to determine the affinity of Abs produced by AFC in an ELISPOT assay. Densely haptenated NP (NP23-BSA)–coated plates are bound by both high and low affinity anti-NP Abs, whereas sparsely haptenated BSA (NP4-BSA)–coated plates are bound only by high affinity anti-NP Abs. Low affinity IgM-producing AFCs in the spleen and BM of Aio−/− mice were within physiological range at 14 d after immunization and declined by day 30 to levels similar to WT (Fig. 1 A). Thus, Aio−/− mice showed no defect in the production of low affinity AFCs during the primary response.

Bottom Line: Lack of Aiolos does not alter expression of any of the previously described factors required for general plasma cell differentiation.No defect in somatic hypermutation, the generation of memory B cells, or short-lived high affinity plasma cells in the spleen was observed upon rechallenge.These studies support a model by which the high affinity plasma cell population in the BM undergoes a unique differentiation program that is dependent on Aiolos.

View Article: PubMed Central - PubMed

Affiliation: Cutaneous Biology Research Center, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA.

ABSTRACT
Antigenic encounter generates long-term immunity sustained by long-lived high affinity plasma cells resident in the bone marrow (BM). Here we show that the Ikaros family member, Aiolos, is specifically required for the generation of these plasma cells. Failure to generate high affinity plasma cells in the BM and to sustain serum antibody titers is apparent after both primary and secondary immunization of Aiolos(-)(/)(-) mice with a range of hapten concentrations. Chimera reconstitutions demonstrate that the BM plasma cell defect is B cell intrinsic. Lack of Aiolos does not alter expression of any of the previously described factors required for general plasma cell differentiation. No defect in somatic hypermutation, the generation of memory B cells, or short-lived high affinity plasma cells in the spleen was observed upon rechallenge. These studies support a model by which the high affinity plasma cell population in the BM undergoes a unique differentiation program that is dependent on Aiolos.

Show MeSH
Related in: MedlinePlus