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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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Examination of plasma cell–enriched populations for activity and expression of supporting factors. (A) FACS® analysis of BM (top) and spleen (bottom) cells from WT and Aio−/− mice 14 d after boost. Cells are gated within the non–B cell lineage compartment and stained with anti-B220 and anti-CD138 Abs. Percentages of plasma cell–like populations (B220− CD138+) are circled and indicated. (B) Sorted B220− CD138+ BM and spleen cells were analyzed by ELISPOT to determine their NP-specific AFC activity. Numbers reflect the amount of NP-specific AFCs per total organ, calculated as the number of AFCs/2,000 sorted and plated B220+ CD138− cells, and adjusted for their percentage as given in A. Total cell counts for WT (open bars) and Aio−/− (solid bars) BM were similar. (C) RT-PCR analysis from sorted CD138+ B220− cells from WT and Aio−/− mice. (i), expression of adhesion molecules CD44, VLA-4, and LFA-1; (ii), chemokine receptors CXCR4, CXCR5, and CCR7; (iii), plasma cell proteins J-chain, Blimp, CD138, IRF-4, XBP, stress response genes Grp94 and Grp78; (iv), Aiolos message as well as B cell gene PAX5 and the actin control.
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fig6: Examination of plasma cell–enriched populations for activity and expression of supporting factors. (A) FACS® analysis of BM (top) and spleen (bottom) cells from WT and Aio−/− mice 14 d after boost. Cells are gated within the non–B cell lineage compartment and stained with anti-B220 and anti-CD138 Abs. Percentages of plasma cell–like populations (B220− CD138+) are circled and indicated. (B) Sorted B220− CD138+ BM and spleen cells were analyzed by ELISPOT to determine their NP-specific AFC activity. Numbers reflect the amount of NP-specific AFCs per total organ, calculated as the number of AFCs/2,000 sorted and plated B220+ CD138− cells, and adjusted for their percentage as given in A. Total cell counts for WT (open bars) and Aio−/− (solid bars) BM were similar. (C) RT-PCR analysis from sorted CD138+ B220− cells from WT and Aio−/− mice. (i), expression of adhesion molecules CD44, VLA-4, and LFA-1; (ii), chemokine receptors CXCR4, CXCR5, and CCR7; (iii), plasma cell proteins J-chain, Blimp, CD138, IRF-4, XBP, stress response genes Grp94 and Grp78; (iv), Aiolos message as well as B cell gene PAX5 and the actin control.

Mentions: Next, we examined the CD138+ B220− population that is enriched in plasma cells. A slight decrease in the number of CD138+ B220− cells was seen in the BM of Aio−/− mice 14 d after secondary immunization, whereas in the spleen there was an increase in this population (Fig. 6 A). ELISPOT analysis of the sorted cells, however, revealed a major deficiency in NP-specific AFC activity when obtained from the BM of Aio−/− mice (Fig. 6 B).


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)

Examination of plasma cell–enriched populations for activity and expression of supporting factors. (A) FACS® analysis of BM (top) and spleen (bottom) cells from WT and Aio−/− mice 14 d after boost. Cells are gated within the non–B cell lineage compartment and stained with anti-B220 and anti-CD138 Abs. Percentages of plasma cell–like populations (B220− CD138+) are circled and indicated. (B) Sorted B220− CD138+ BM and spleen cells were analyzed by ELISPOT to determine their NP-specific AFC activity. Numbers reflect the amount of NP-specific AFCs per total organ, calculated as the number of AFCs/2,000 sorted and plated B220+ CD138− cells, and adjusted for their percentage as given in A. Total cell counts for WT (open bars) and Aio−/− (solid bars) BM were similar. (C) RT-PCR analysis from sorted CD138+ B220− cells from WT and Aio−/− mice. (i), expression of adhesion molecules CD44, VLA-4, and LFA-1; (ii), chemokine receptors CXCR4, CXCR5, and CCR7; (iii), plasma cell proteins J-chain, Blimp, CD138, IRF-4, XBP, stress response genes Grp94 and Grp78; (iv), Aiolos message as well as B cell gene PAX5 and the actin control.
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Related In: Results  -  Collection

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fig6: Examination of plasma cell–enriched populations for activity and expression of supporting factors. (A) FACS® analysis of BM (top) and spleen (bottom) cells from WT and Aio−/− mice 14 d after boost. Cells are gated within the non–B cell lineage compartment and stained with anti-B220 and anti-CD138 Abs. Percentages of plasma cell–like populations (B220− CD138+) are circled and indicated. (B) Sorted B220− CD138+ BM and spleen cells were analyzed by ELISPOT to determine their NP-specific AFC activity. Numbers reflect the amount of NP-specific AFCs per total organ, calculated as the number of AFCs/2,000 sorted and plated B220+ CD138− cells, and adjusted for their percentage as given in A. Total cell counts for WT (open bars) and Aio−/− (solid bars) BM were similar. (C) RT-PCR analysis from sorted CD138+ B220− cells from WT and Aio−/− mice. (i), expression of adhesion molecules CD44, VLA-4, and LFA-1; (ii), chemokine receptors CXCR4, CXCR5, and CCR7; (iii), plasma cell proteins J-chain, Blimp, CD138, IRF-4, XBP, stress response genes Grp94 and Grp78; (iv), Aiolos message as well as B cell gene PAX5 and the actin control.
Mentions: Next, we examined the CD138+ B220− population that is enriched in plasma cells. A slight decrease in the number of CD138+ B220− cells was seen in the BM of Aio−/− mice 14 d after secondary immunization, whereas in the spleen there was an increase in this population (Fig. 6 A). ELISPOT analysis of the sorted cells, however, revealed a major deficiency in NP-specific AFC activity when obtained from the BM of Aio−/− mice (Fig. 6 B).

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