IL2RB/IL2RG: A common receptor subunit driving signaling for IL-2 and IL-15. 

• Gene Information: IL2RB (chromosome 22q12) encodes the IL-2 receptor beta subunit, while IL2RG (chromosome Xq13) encodes the common gamma chain, an essential component shared by multiple interleukin receptor complexes. 
• Protein Expression: Both proteins are constitutively or inducibly expressed on natural killer (NK) cells, T lymphocytes, and macrophages, orchestrating critical survival and expansion signals during lymphoid development. 
• Signaling Pathway: Together with IL-2RA, these subunits form high-affinity complexes that bind IL-2, activating downstream JAK1/JAK3 tyrosine kinases and triggering the proliferative STAT3/STAT5, PI3K/AKT, and MAPK signaling pathways. 
• Therapeutic Inhibition: Targeting the IL2RB/IL2RG complex or its downstream cascades helps treat autoimmune disorders and graft-versus-host disease, while optimizing this axis enhances adoptive cell therapies for cancer immunotherapy.

IL2RB Exons 2-8 of mouse Il2rb gene that encode extracellular domain were replaced by human counterparts in B-hIL2RB/hIL2RG mice. 

The genomic region of mouse IL2RB/hIL2RG gene that encodes signal peptide, transmembrane domain and cytoplasmic portion was retained. The promoter, 5’UTR and 3’UTR region of the mouse gene were also retained. The chimeric IL2RB expression was driven by endogenous mouse Il2rb promoter, while mouse Il2rb gene transcription and translation will be disrupted. IL2RG Exons 1–8 of the mouse Il2rg gene that encode the entire protein (from ATG to stop codon) were replaced with the corresponding human sequences in B-hIL2RB/hIL2RG mice. The endogenous mouse promoter, 5′ UTR, and 3′ UTR regions were retained, allowing human IL2RG expression to be driven by the native mouse Il2rg promoter, while endogenous mouse Il2rg transcription and translation are abolished. B-hIL2RB/hIL2RG mice (111850) were obtained by mating B-hIL2RB mice (110737) and B-hIL2RG mice (110087).

Strain specific IL2RB and IL2RG expression analysis in wild-type C57BL/6 mice and homozygous humanized B-hIL2RB/hIL2RG mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6 mice (+/+; +/+), heterozygous B-hIL2RB/hIL2RG mice (H/+; H/+) and homozygous B-hIL2RB/hIL2RG mice (H/H; H/H) stimulated with anti-mouse CD3ε antibody (7.5 μg, i.p.) for 24 hours. Protein expression was analyzed with anti-mouse IL2RB antibody (Biolegend, 105911), anti-human IL2RB antibody (Biolegend, 339005), anti-mouse IL2RG antibody (Biolegend, 132307), and anti-human IL2RG antibody (Biolegend, 338605) by flow cytometry.

Strain specific IL2RB and IL2RG expression analysis in wild-type C57BL/6 mice and homozygous humanized B-hIL2RB/hIL2RG mice by flow cytometry. Splenocytes were collected from wild-type C57BL/6 mice (+/+; +/+), heterozygous B-hIL2RB/hIL2RG mice (H/+; H/+) and homozygous B-hIL2RB/hIL2RG mice (H/H; H/H) stimulated with anti-mouse CD3ε antibody (7.5 μg, i.p.) for 24 hours. Protein expression was analyzed with anti-mouse IL2RB antibody (Biolegend, 105911), anti-human IL2RB antibody (Biolegend, 339005), anti-mouse IL2RG antibody (Biolegend, 132307), and anti-human IL2RG antibody (Biolegend, 338605) by flow cytometry.

Phosphorylation of STAT5 induction by human IL2 and complex of IL15/IL15RA in wild-type C57BL/6 mice and B-hIL2RB/hIL2RG mice. Splenocytes were collected from wild-type C57BL/6 mice, heterozygous B-hIL2RB/hIL2RG mice and homozygous a B-hIL2RB/hIL2RG mice, and stimulated with human IL2 or complex of IL15/IL15RA in vitro for 30 min. Then cells were analyzed by flow cytometry with anti-pSTAT5 antibodies.

Analysis of leukocyte subpopulations by flow cytometry in immune organs and blood. Splenocytes, peripheral blood, and lymph nodes were isolated from wild-type C57BL/6 mice (+/+; +/+), heterozygous B-hIL2RB/hIL2RG mice (H/+; H/+) and homozygous B-hIL2RB/hIL2RG mice (H/H; H/H) (female, 6-week-old, n = 3). Single live cells were gated on the CD45⁺ population and analyzed by flow cytometry as indicated. Values are expressed as mean ± SEM. Significance is determined by two-way ANOVA test. *P < 0.05, **P < 0.01, ***P < 0.001.

Analysis of T-cell subpopulations by flow cytometry in immune organs and blood. Splenocytes, peripheral blood, and lymph nodes were isolated from wild-type C57BL/6 mice (+/+; +/+), heterozygous B-hIL2RB/hIL2RG mice (H/+; H/+) and homozygous B-hIL2RB/hIL2RG mice (H/H; H/H) (female, 6-week-old, n = 3). Single live cells were gated on the TCRβ⁺ T-cell population and analyzed by flow cytometry as indicated. Values are expressed as mean ± SEM.

Antitumor activity of IL2 analog (provided by the client) in B-hIL2RB/hIL2RG mice. (A) Tumor growth curves. (B) Body weight changes during treatment. The tumor growth curve of individual mice in PBS group (C) and IL2 analog (provided by the client) treatment group (D). Values are expressed as mean ± SEM.