Abstract
Splenic transitional B-cells (T1 and T2) are selected to avoid self-reactivity and to safeguard against autoimmunity, then differentiate into mature follicular (FO-I and FO-II) and marginal zone (MZ) subsets. Transcriptomic analysis by RNA-seq of the five B-cell subsets revealed T1 cell signature genes included RAG suggesting a potential for receptor revision. T1 to T2 B-cell differentiation was marked by a switch from Myb to Myc, increased expression of the PI3K adapter DAP10 and MHC class II. FO-II may be an intermediate in FO-I differentiation and may also become MZ B-cells as suggested by principle component analysis. MZ B-cells possessed the most distinct transcriptome including down-regulation of CD45 phosphatase-associated protein (CD45-AP/PTPRC-AP), as well as upregulation of IL-9R and innate molecules TLR3, TLR7, and bactericidal Perforin-2 (MPEG1). Among the endosomal TLRs, stimulation via TLR3 further enhanced Perforin-2 expression exclusively in MZ B-cells. Using gene-deleted and overexpressing transgenic mice we show that IL-9/IL-9R interaction resulted in rapid activation of STAT1, 3, and 5, primarily in MZ B-cells. Importantly, CD45-AP mutant mice had reduced transitional and increased mature MZ and FO B-cells, suggesting that it prevents premature entry of transitional B-cells to the mature B-cell pool or their survival and proliferation. Together, these findings suggest, developmental plasticity among splenic B-cell subsets, potential for receptor revision in peripheral tolerance whereas enhanced metabolism coincides with T2 to mature B-cell differentiation. Further, unique core transcriptional signatures in MZ B-cells may control their innate features.
| Original language | English (US) |
|---|---|
| Article number | 00030 |
| Journal | Frontiers in Immunology |
| Volume | 6 |
| Issue number | FEB |
| DOIs | |
| State | Published - 2015 |
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Keywords
- DAP10 PI3K pathway
- Follicular 1 and 2 B-cells
- IL-9/IL-9R
- Marginal zone B-cells
- Myb Myc
- Splenic transitional B-cells
- Toll-like receptors 3 and 7
- Transcriptome by RNA-seq technique
ASJC Scopus subject areas
- Immunology
- Immunology and Allergy
Cite this
Distinct transcriptomic features are associated with transitional and mature B-cell populations in the mouse spleen. / Kleiman, Eden; Salyakina, Daria; De Heusch, Magali; Hoek, Kristen L.; Llanes, Joan M.; Castro, Iris; Wright, Jacqueline A.; Clark, Emily S.; Dykxhoorn, Derek M; Capobianco, Enrico; Takeda, Akiko; Renauld, Jean Christophe; Khan, Wasif.
In: Frontiers in Immunology, Vol. 6, No. FEB, 00030, 2015.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Distinct transcriptomic features are associated with transitional and mature B-cell populations in the mouse spleen
AU - Kleiman, Eden
AU - Salyakina, Daria
AU - De Heusch, Magali
AU - Hoek, Kristen L.
AU - Llanes, Joan M.
AU - Castro, Iris
AU - Wright, Jacqueline A.
AU - Clark, Emily S.
AU - Dykxhoorn, Derek M
AU - Capobianco, Enrico
AU - Takeda, Akiko
AU - Renauld, Jean Christophe
AU - Khan, Wasif
PY - 2015
Y1 - 2015
N2 - Splenic transitional B-cells (T1 and T2) are selected to avoid self-reactivity and to safeguard against autoimmunity, then differentiate into mature follicular (FO-I and FO-II) and marginal zone (MZ) subsets. Transcriptomic analysis by RNA-seq of the five B-cell subsets revealed T1 cell signature genes included RAG suggesting a potential for receptor revision. T1 to T2 B-cell differentiation was marked by a switch from Myb to Myc, increased expression of the PI3K adapter DAP10 and MHC class II. FO-II may be an intermediate in FO-I differentiation and may also become MZ B-cells as suggested by principle component analysis. MZ B-cells possessed the most distinct transcriptome including down-regulation of CD45 phosphatase-associated protein (CD45-AP/PTPRC-AP), as well as upregulation of IL-9R and innate molecules TLR3, TLR7, and bactericidal Perforin-2 (MPEG1). Among the endosomal TLRs, stimulation via TLR3 further enhanced Perforin-2 expression exclusively in MZ B-cells. Using gene-deleted and overexpressing transgenic mice we show that IL-9/IL-9R interaction resulted in rapid activation of STAT1, 3, and 5, primarily in MZ B-cells. Importantly, CD45-AP mutant mice had reduced transitional and increased mature MZ and FO B-cells, suggesting that it prevents premature entry of transitional B-cells to the mature B-cell pool or their survival and proliferation. Together, these findings suggest, developmental plasticity among splenic B-cell subsets, potential for receptor revision in peripheral tolerance whereas enhanced metabolism coincides with T2 to mature B-cell differentiation. Further, unique core transcriptional signatures in MZ B-cells may control their innate features.
AB - Splenic transitional B-cells (T1 and T2) are selected to avoid self-reactivity and to safeguard against autoimmunity, then differentiate into mature follicular (FO-I and FO-II) and marginal zone (MZ) subsets. Transcriptomic analysis by RNA-seq of the five B-cell subsets revealed T1 cell signature genes included RAG suggesting a potential for receptor revision. T1 to T2 B-cell differentiation was marked by a switch from Myb to Myc, increased expression of the PI3K adapter DAP10 and MHC class II. FO-II may be an intermediate in FO-I differentiation and may also become MZ B-cells as suggested by principle component analysis. MZ B-cells possessed the most distinct transcriptome including down-regulation of CD45 phosphatase-associated protein (CD45-AP/PTPRC-AP), as well as upregulation of IL-9R and innate molecules TLR3, TLR7, and bactericidal Perforin-2 (MPEG1). Among the endosomal TLRs, stimulation via TLR3 further enhanced Perforin-2 expression exclusively in MZ B-cells. Using gene-deleted and overexpressing transgenic mice we show that IL-9/IL-9R interaction resulted in rapid activation of STAT1, 3, and 5, primarily in MZ B-cells. Importantly, CD45-AP mutant mice had reduced transitional and increased mature MZ and FO B-cells, suggesting that it prevents premature entry of transitional B-cells to the mature B-cell pool or their survival and proliferation. Together, these findings suggest, developmental plasticity among splenic B-cell subsets, potential for receptor revision in peripheral tolerance whereas enhanced metabolism coincides with T2 to mature B-cell differentiation. Further, unique core transcriptional signatures in MZ B-cells may control their innate features.
KW - DAP10 PI3K pathway
KW - Follicular 1 and 2 B-cells
KW - IL-9/IL-9R
KW - Marginal zone B-cells
KW - Myb Myc
KW - Splenic transitional B-cells
KW - Toll-like receptors 3 and 7
KW - Transcriptome by RNA-seq technique
UR - http://www.scopus.com/inward/record.url?scp=84926649961&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84926649961&partnerID=8YFLogxK
U2 - 10.3389/fimmu.2015.00030
DO - 10.3389/fimmu.2015.00030
M3 - Article
AN - SCOPUS:84926649961
VL - 6
JO - Frontiers in Immunology
JF - Frontiers in Immunology
SN - 1664-3224
IS - FEB
M1 - 00030
ER -