CD86 is expressed on murine hematopoietic stem cells and denotes lymphopoietic potential

Abstract

IntroductionA large body of information exists about molecular mechanisms involved in maintaining HSC integrity, and many studies have identified unique markers associated with differentiation. 1 However, several of these parameters differ between strains of mice or change dramatically according to developmental age, activation status, or inflammation. [2][3][4] This issue gained importance with the realization that HSCs are normally heterogeneous and that functionally distinct subsets can be resolved according to phenotypes. [5][6][7][8] As one example, we discovered that a unique population of lineage marker Ϫ Sca-1 ϩ c-Kit ϩ (LSK) CD150 ϩ CD48 Ϫ HSCs lacked CD86. 9 CD86 Ϫ HSCs accumulated in old mice as well as young mice repeatedly injected with lipopolysaccharide (LPS). At least some HSCs in those animals had low ability to self-renew and restore the adaptive immune system when transplanted. In addition, HSCs in the chronically stimulated animals were abnormally in cycle. 9 However, the relation between those phenomena and CD86 loss was unclear.B7-1 (CD80) and B7-2 (CD86) are type I transmembrane proteins that were originally identified as ligands for CD28/CTLA-4. 10 Murine CD80 and CD86 share ϳ 28% amino acid identity, but both are capable of using conserved binding sites to recognize either human or mouse CD28. Although this is important for T-cell activation, another ligand, CTLA-4 functions as an inhibitory receptor for immune responses. 11 CD86 is constitutively expressed on dendritic cells, B cells, and thymic epithelial cells. CD80 is only expressed by activated B and T cells. Several reports suggest that CD80 and CD86 have overlapping functions because double knockout (KO) mice have more severe defects in immune responses than single KOs. 12 However, one report suggests there are differential functions. 13 Given the importance of CD80/86 for T-cell activation, blocking Abs are valuable in establishing tolerance during BM transplantation. 14 Marrow stromal cells express the CD28 ligand in close proximity to B-lineage progenitors, and CD28 might slightly enhance B lymphopoiesis. 15 CD86 is expressed by many HSCs, 7,9 but gain or loss relative to hematopoiesis has not been explored. We now report that CD86 loss on stem and progenitor cells closely parallels their loss of lymphopoietic potential. It is a uniquely useful marker for appreciating functional heterogeneity among HSCs that are otherwise similar. MethodsMice C57BL/6 (CD45.2 alloantigen), CD86-deficient (CD86 Ϫ/Ϫ ), and B6-SJL/ Ly5.1 (CD45.1 alloantigen) mice were purchased from The Jackson Laboratory. C57BL/6 ϫ SJL/Ly5.1 F 1 (CD45.1 and CD45.2 alloantigens) and RAG1/GFP (recombinase activator gene 1/green fluorescent protein) knock-in mice were bred and maintained in the Laboratory Animal Resource Center at the Oklahoma Medical Research Foundation. PU.1 fl/fl and C/EBP␣ fl/fl mice were bred with Mx1 Cre mice to generate PU.1 fl/fl or C/EBP␣ fl/fl ϪMx1 Cre mice. Those and C/EBP␤KO mice were bred and maintained in Beth Israel Deaconess Medical C...

CD41 expression marks myeloid-biased adult hematopoietic stem cells and increases with age

“…4 In contrast, CD412 HSCs were found to be enriched for lymphoid-associated factors such as ikzf1, ikzf2, notch1, notch2, flt3, and il7ra, as well as CD86, which has been recently found to denote lymphopoietic potential of HSCs. 41 Analysis of HSC lineage bias in vivo confirmed the observations that CD41 marks myeloid-biased HSCs. The fact that the lineage distribution differences between CD41:YFP1 and CD41:YFP2 fractions were less evident in secondary recipients could have several interpretations.…”

The Satb1 Protein Directs Hematopoietic Stem Cell Differentiation toward Lymphoid Lineages

“…Interestingly, among lymphoid-related genes, Rag1 , which is indispensable for both T and B cell differentiation, was strongly induced by Satb1 (Figure 5C). Expression of the CD86 gene that correlates with lymphoid competency (Shimazu et al, 2012) was also significantly elevated.…”

Stem and Progenitor Cell Subsets Are Affected by JAK2 Signaling and Can Be Monitored by Flow Cytometry

“…Our prior studies indicated that loss of CD86 and CD18 together with increases in CD41 and CD150 defines HSC that accumulate in aged or chronically LPS treated animals [15], [16]. Even in untreated adult mice, such HSC are poor with respect to lymphocyte formation and probably overlap with myeloid-skewed HSC identified in single cell transplantation experiments [5]–[7].…”