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c-Myb is required for plasma cell migration to bone marrow after immunization or infection.

Good-Jacobson KL, O'Donnell K, Belz GT, Nutt SL, Tarlinton DM - J. Exp. Med. (2015)

Bottom Line: Here, we detail the critical role of the transcription factor c-Myb in determining plasma cell location.This was correlated with a dramatic reduction of plasma cells in peripheral blood, mislocalization in spleen, and an inability of c-Myb-deficient plasma cells to migrate along a CXCL12 gradient.Therefore, c-Myb plays an essential, novel role in establishing the long-lived plasma cell population in the BM via responsiveness to chemokine migration cues.

View Article: PubMed Central - HTML - PubMed

Affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia jacobson@wehi.edu.au tarlinton@wehi.edu.au.

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Altered plasma cell populations within secondary lymphoid organs. (A and B) CD138hi GFP populations in unimmunized c-Mybfl/fl and c-Mybfl/flCd23Cre/+ mice. c-Mybfl/fl or c-Mybfl/flCd23Cre/+ mice with gfp introduced into the Blimp-1 locus on one allele were used to track Blimp-1–expressing CD138hi cells in spleen, BM, and MLN. (B) Frequency of Blimp-1hiCD138hi and Blimp-1intCD138hi cells. n ≥ 4 mice per organ, combined from two independent experiments. (C–E) CD138hi GFP cells were sort-purified from the BM of c-Mybfl/fl and c-Mybfl/flCd23Cre/+ mice (n = 3 per genotype) and pooled for sequencing. (C) Cumulative frequency of VH mutations in BM Blimp-1hiCD138hi cells and (D) number versus frequency of VH mutations in BM Blimp-1hiCD138hi cells. (E–F) Cd23Cre/+ and c-Mybfl/flCd23Cre/+ were immunized with CGG in alum and ELISPOT analysis of IgM+ (E) and IgG1+ (F) CGG-specific BM ASCs was performed at 14 and 29 d after immunization (n = 4 mice per genotype per time point). *, P < 0.05.
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fig4: Altered plasma cell populations within secondary lymphoid organs. (A and B) CD138hi GFP populations in unimmunized c-Mybfl/fl and c-Mybfl/flCd23Cre/+ mice. c-Mybfl/fl or c-Mybfl/flCd23Cre/+ mice with gfp introduced into the Blimp-1 locus on one allele were used to track Blimp-1–expressing CD138hi cells in spleen, BM, and MLN. (B) Frequency of Blimp-1hiCD138hi and Blimp-1intCD138hi cells. n ≥ 4 mice per organ, combined from two independent experiments. (C–E) CD138hi GFP cells were sort-purified from the BM of c-Mybfl/fl and c-Mybfl/flCd23Cre/+ mice (n = 3 per genotype) and pooled for sequencing. (C) Cumulative frequency of VH mutations in BM Blimp-1hiCD138hi cells and (D) number versus frequency of VH mutations in BM Blimp-1hiCD138hi cells. (E–F) Cd23Cre/+ and c-Mybfl/flCd23Cre/+ were immunized with CGG in alum and ELISPOT analysis of IgM+ (E) and IgG1+ (F) CGG-specific BM ASCs was performed at 14 and 29 d after immunization (n = 4 mice per genotype per time point). *, P < 0.05.

Mentions: To further investigate the ASC defect, c-Mybfl/flCd23Cre/+ mice were crossed with Blimp-1gfp/+ reporter mice (Kallies et al., 2004), within which plasma cell populations can be divided into Blimp-1int and Blimp-1hi populations that have distinct characteristics (Kallies et al., 2004). Blimp-1int plasma cells are short-lived, less mature plasma cells, which is the population that retains migratory potential (Hauser et al., 2002). c-Mybfl/flCd23Cre/+ or c-Mybfl/fl littermates that were Blimp-1gfp/+ were used to track Blimp-1intCD138hi plasmablasts and Blimp-1hiCD138hi plasma cells. Whereas both populations still existed in the BM, mesenteric lymph nodes (MLNs), and spleen, there was a significant increase in Blimp-1int plasmablasts in the absence of c-Myb (Fig. 4, A and B). Furthermore, the majority of BM B220loCD138hi cells were IgM (mean ± SEM: 81 ± 3% versus 34 ± 1.7% in controls), indicating a different route of formation.


c-Myb is required for plasma cell migration to bone marrow after immunization or infection.

Good-Jacobson KL, O'Donnell K, Belz GT, Nutt SL, Tarlinton DM - J. Exp. Med. (2015)

Altered plasma cell populations within secondary lymphoid organs. (A and B) CD138hi GFP populations in unimmunized c-Mybfl/fl and c-Mybfl/flCd23Cre/+ mice. c-Mybfl/fl or c-Mybfl/flCd23Cre/+ mice with gfp introduced into the Blimp-1 locus on one allele were used to track Blimp-1–expressing CD138hi cells in spleen, BM, and MLN. (B) Frequency of Blimp-1hiCD138hi and Blimp-1intCD138hi cells. n ≥ 4 mice per organ, combined from two independent experiments. (C–E) CD138hi GFP cells were sort-purified from the BM of c-Mybfl/fl and c-Mybfl/flCd23Cre/+ mice (n = 3 per genotype) and pooled for sequencing. (C) Cumulative frequency of VH mutations in BM Blimp-1hiCD138hi cells and (D) number versus frequency of VH mutations in BM Blimp-1hiCD138hi cells. (E–F) Cd23Cre/+ and c-Mybfl/flCd23Cre/+ were immunized with CGG in alum and ELISPOT analysis of IgM+ (E) and IgG1+ (F) CGG-specific BM ASCs was performed at 14 and 29 d after immunization (n = 4 mice per genotype per time point). *, P < 0.05.
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fig4: Altered plasma cell populations within secondary lymphoid organs. (A and B) CD138hi GFP populations in unimmunized c-Mybfl/fl and c-Mybfl/flCd23Cre/+ mice. c-Mybfl/fl or c-Mybfl/flCd23Cre/+ mice with gfp introduced into the Blimp-1 locus on one allele were used to track Blimp-1–expressing CD138hi cells in spleen, BM, and MLN. (B) Frequency of Blimp-1hiCD138hi and Blimp-1intCD138hi cells. n ≥ 4 mice per organ, combined from two independent experiments. (C–E) CD138hi GFP cells were sort-purified from the BM of c-Mybfl/fl and c-Mybfl/flCd23Cre/+ mice (n = 3 per genotype) and pooled for sequencing. (C) Cumulative frequency of VH mutations in BM Blimp-1hiCD138hi cells and (D) number versus frequency of VH mutations in BM Blimp-1hiCD138hi cells. (E–F) Cd23Cre/+ and c-Mybfl/flCd23Cre/+ were immunized with CGG in alum and ELISPOT analysis of IgM+ (E) and IgG1+ (F) CGG-specific BM ASCs was performed at 14 and 29 d after immunization (n = 4 mice per genotype per time point). *, P < 0.05.
Mentions: To further investigate the ASC defect, c-Mybfl/flCd23Cre/+ mice were crossed with Blimp-1gfp/+ reporter mice (Kallies et al., 2004), within which plasma cell populations can be divided into Blimp-1int and Blimp-1hi populations that have distinct characteristics (Kallies et al., 2004). Blimp-1int plasma cells are short-lived, less mature plasma cells, which is the population that retains migratory potential (Hauser et al., 2002). c-Mybfl/flCd23Cre/+ or c-Mybfl/fl littermates that were Blimp-1gfp/+ were used to track Blimp-1intCD138hi plasmablasts and Blimp-1hiCD138hi plasma cells. Whereas both populations still existed in the BM, mesenteric lymph nodes (MLNs), and spleen, there was a significant increase in Blimp-1int plasmablasts in the absence of c-Myb (Fig. 4, A and B). Furthermore, the majority of BM B220loCD138hi cells were IgM (mean ± SEM: 81 ± 3% versus 34 ± 1.7% in controls), indicating a different route of formation.

Bottom Line: Here, we detail the critical role of the transcription factor c-Myb in determining plasma cell location.This was correlated with a dramatic reduction of plasma cells in peripheral blood, mislocalization in spleen, and an inability of c-Myb-deficient plasma cells to migrate along a CXCL12 gradient.Therefore, c-Myb plays an essential, novel role in establishing the long-lived plasma cell population in the BM via responsiveness to chemokine migration cues.

View Article: PubMed Central - HTML - PubMed

Affiliation: Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria 3052, Australia Department of Medical Biology, University of Melbourne, Parkville, Victoria 3010, Australia jacobson@wehi.edu.au tarlinton@wehi.edu.au.

Show MeSH
Related in: MedlinePlus