Limits...
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.

Show MeSH

Related in: MedlinePlus

Antigenic reexposure supports transient expansion of high affinity AFCs in the spleen but not in the BM. FACS® analysis of spleen cells from WT and Aio−/− mice before and 6 d after secondary immunization (A). Cells were gated within the lineage-negative compartment and examined for NP binding and expression of Ig light chain. (B) Frequencies of NP-specific IgG1-producing AFCs in the spleen (left) and BM (right) of WT (○) and Aio−/− (•) mice were examined at 6 and 14 d after boost. Data were obtained from ELISPOT assays using NP4 (high affinity) and NP23 (total) as the coating Ags. Each point represents an individual mouse and data is from one experiment of at least three with similar results. (C) BM NP-specific AFCs of IgE, IgA and IgG isotypes, IgG1 isotype, and IgM isotype were quantified 14 d after 2° immunization. High and low affinity anti-NP AFC (NP23 binding) are represented by open bars. High affinity (NP4 binding) anti-NP AFCs comprise the hatched and solid portion of the bars.
© Copyright Policy
Related In: Results  -  Collection


getmorefigures.php?uid=PMC2211773&req=5

fig2: Antigenic reexposure supports transient expansion of high affinity AFCs in the spleen but not in the BM. FACS® analysis of spleen cells from WT and Aio−/− mice before and 6 d after secondary immunization (A). Cells were gated within the lineage-negative compartment and examined for NP binding and expression of Ig light chain. (B) Frequencies of NP-specific IgG1-producing AFCs in the spleen (left) and BM (right) of WT (○) and Aio−/− (•) mice were examined at 6 and 14 d after boost. Data were obtained from ELISPOT assays using NP4 (high affinity) and NP23 (total) as the coating Ags. Each point represents an individual mouse and data is from one experiment of at least three with similar results. (C) BM NP-specific AFCs of IgE, IgA and IgG isotypes, IgG1 isotype, and IgM isotype were quantified 14 d after 2° immunization. High and low affinity anti-NP AFC (NP23 binding) are represented by open bars. High affinity (NP4 binding) anti-NP AFCs comprise the hatched and solid portion of the bars.

Mentions: To determine whether memory B cell formation was affected in Aio−/− mice, the frequency of NP-binding Igλ+ B lymphocytes was analyzed by flow cytometry 6 d after boost. Although NP-specific B cells were undetectable before immunization, they were present at similar numbers in WT and Aio−/− spleens (Fig. 2 A) and BM (not depicted) after secondary immunization. These cells do not express CD138 or other plasma cell markers (not depicted).


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)

Antigenic reexposure supports transient expansion of high affinity AFCs in the spleen but not in the BM. FACS® analysis of spleen cells from WT and Aio−/− mice before and 6 d after secondary immunization (A). Cells were gated within the lineage-negative compartment and examined for NP binding and expression of Ig light chain. (B) Frequencies of NP-specific IgG1-producing AFCs in the spleen (left) and BM (right) of WT (○) and Aio−/− (•) mice were examined at 6 and 14 d after boost. Data were obtained from ELISPOT assays using NP4 (high affinity) and NP23 (total) as the coating Ags. Each point represents an individual mouse and data is from one experiment of at least three with similar results. (C) BM NP-specific AFCs of IgE, IgA and IgG isotypes, IgG1 isotype, and IgM isotype were quantified 14 d after 2° immunization. High and low affinity anti-NP AFC (NP23 binding) are represented by open bars. High affinity (NP4 binding) anti-NP AFCs comprise the hatched and solid portion of the bars.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2211773&req=5

fig2: Antigenic reexposure supports transient expansion of high affinity AFCs in the spleen but not in the BM. FACS® analysis of spleen cells from WT and Aio−/− mice before and 6 d after secondary immunization (A). Cells were gated within the lineage-negative compartment and examined for NP binding and expression of Ig light chain. (B) Frequencies of NP-specific IgG1-producing AFCs in the spleen (left) and BM (right) of WT (○) and Aio−/− (•) mice were examined at 6 and 14 d after boost. Data were obtained from ELISPOT assays using NP4 (high affinity) and NP23 (total) as the coating Ags. Each point represents an individual mouse and data is from one experiment of at least three with similar results. (C) BM NP-specific AFCs of IgE, IgA and IgG isotypes, IgG1 isotype, and IgM isotype were quantified 14 d after 2° immunization. High and low affinity anti-NP AFC (NP23 binding) are represented by open bars. High affinity (NP4 binding) anti-NP AFCs comprise the hatched and solid portion of the bars.
Mentions: To determine whether memory B cell formation was affected in Aio−/− mice, the frequency of NP-binding Igλ+ B lymphocytes was analyzed by flow cytometry 6 d after boost. Although NP-specific B cells were undetectable before immunization, they were present at similar numbers in WT and Aio−/− spleens (Fig. 2 A) and BM (not depicted) after secondary immunization. These cells do not express CD138 or other plasma cell markers (not depicted).

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