Distinct transcriptomic features are associated with transitional and mature B-cell populations in the mouse spleen

Eden Kleiman, Daria Salyakina, Magali De Heusch, Kristen L. Hoek, Joan M. Llanes, Iris Castro, Jacqueline A. Wright, Emily S. Clark, Derek M Dykxhoorn, Enrico Capobianco, Akiko Takeda, Jean Christophe Renauld, Wasif Khan

Research output: Contribution to journalArticle

15 Scopus citations

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 languageEnglish (US)
Article number00030
JournalFrontiers in Immunology
Volume6
Issue numberFEB
DOIs
StatePublished - 2015

    Fingerprint

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

Kleiman, E., Salyakina, D., De Heusch, M., Hoek, K. L., Llanes, J. M., Castro, I., Wright, J. A., Clark, E. S., Dykxhoorn, D. M., Capobianco, E., Takeda, A., Renauld, J. C., & Khan, W. (2015). Distinct transcriptomic features are associated with transitional and mature B-cell populations in the mouse spleen. Frontiers in Immunology, 6(FEB), [00030]. https://doi.org/10.3389/fimmu.2015.00030