Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2022 Sep 21;6(10):e774.
doi: 10.1097/HS9.0000000000000774. eCollection 2022 Oct.

Heterozygous Variants in the DNA-binding Domain of c-Myb May Affect Normal B/T Cell Development

Bas M Smits  1   2 , Taila Hartley  3 , Ester Dünnebach  2 , Marije Bartels  4 , Kim M Boycott  3   5 , Kirstin D Kernohan  3   6 , David A Dyment  3   5 , Jacques C Giltay  7 , Elie Haddad  8 , Olga Jarinova  3   5 , Joris van Montfrans  1 , Annet van Royen-Kerkhof  1 , Lars T van der Veken  7 , Moniek de Witte  9 , Stefan Nierkens  2   10 , Anne Pham-Huy  3   5 , Helen L Leavis  11
Affiliations

Heterozygous Variants in the DNA-binding Domain of c-Myb May Affect Normal B/T Cell Development

Bas M Smits et al. Hemasphere. .
No abstract available

PubMed Disclaimer

Figures

Figure 1.
Figure 1.
c-Myb and its downstream targets are differently expressed in 2 technical replicates of T cells carrying the p.Lys182Arg variant. Results were analyzed with 2-tailed Student t tests, *P < 0.05 **P < 0.01. (A), In activated mice CD8+ T cells, transcription factor c-Myb has been found to increase Tcf7 and Bcl2 expression, while repressing Zeb2 expression through competitive binding to the promoter. (B), Proportions of CD3+ subsets in the patient vs 3 healthy controls showing that the patient has reduced naive CD3+ fractions and increased TEMRA fractions. (C), Expression of levels of c-Myb, Tcf7, Bcl2, and Zeb2 in unstimulated T cells. 2^–ΔΔCt values were obtained using the mean ΔCt values of the healthy controls. Zeb2 expression is higher in patient samples. (D), Peak c-Myb, Tcf7, and Bcl2 expression and Zeb2 repression in T cells after stimulation. 2^–ΔΔCt values were obtained using the mean ΔCt values of unstimulated T cells. Patient cells show a trend towards decreased c-Myb, Tcf7, and Bcl2 expression and similar Zeb2 expression. (E–G), MFI of c-Myb, Tcf7, and Zeb2 in CD3+, CD4+, and CD8+ cells. Peak protein expression of both c-Myb and Tcf7 was lower in CD3+ and CD8+ cells but not in CD4+ cells. MFI = mean fluorescence intensity; TEMRA = T effector memory cells expressing CD45RA.
See this image and copyright information in PMC

References

    1. Tangye SG, Al-Herz W, Bousfiha A, et al. Human inborn errors of immunity: 2022 update on the classification from the International Union of Immunological Societies Expert Committee. J Clin Immunol. 2022 June 24.. [Epub ahead of print]. - PMC - PubMed
    1. Smits BM, Lelieveld PHC, Ververs FA, et al. A dominant activating RAC2 variant associated with immunodeficiency and pulmonary disease. Clin Immunol. 2020;212:108248. - PubMed
    1. Greig KT, de Graaf CA, Murphy JM, et al. Critical roles for c-Myb in lymphoid priming and early B-cell development. Blood. 2010;115:2796–2805. - PMC - PubMed
    1. Fahl SP, Daamen AR, Crittenden RB, et al. c-Myb coordinates survival and the expression of genes that are critical for the pre-BCR checkpoint. J Immunol. 2018;200:3450–3463. - PMC - PubMed
    1. Gautam S, Fioravanti J, Zhu W, et al. The transcription factor c-Myb regulates CD8+ T cell stemness and antitumor immunity. Nat Immunol. 2019;20:337–349. - PMC - PubMed