Helix-Loop-Helix Proteins in Adaptive Immune Development

Overview

Journal Front Immunol

Specialty Allergy & Immunology

Date 2022 May 31

PMID 35634342

Authors

Megan Aubrey

Zachary J Warburg

Cornelis Murre

Affiliations

Soon will be listed here.

Abstract

The E/ID protein axis is instrumental for defining the developmental progression and functions of hematopoietic cells. The E proteins are dimeric transcription factors that activate gene expression programs and coordinate changes in chromatin organization. Id proteins are antagonists of E protein activity. Relative levels of E/Id proteins are modulated throughout hematopoietic development to enable the progression of hematopoietic stem cells into multiple adaptive and innate immune lineages including natural killer cells, B cells and T cells. In early progenitors, the E proteins promote commitment to the T and B cell lineages by orchestrating lineage specific programs of gene expression and regulating VDJ recombination of antigen receptor loci. In mature B cells, the E/Id protein axis functions to promote class switch recombination and somatic hypermutation. E protein activity further regulates differentiation into distinct CD4+ and CD8+ T cells subsets and instructs mature T cell immune responses. In this review, we discuss how the E/Id proteins define the adaptive immune system lineages, focusing on their role in directing developmental gene programs.

Citing Articles

TCF1 dosage determines cell fate during T cell development.

Verma A, Aylward B, Ma F, Sherman C, Chopp L, Shinton S Sci Adv. 2024; 10(48):eado5982.

PMID: 39602533 PMC: 11601199. DOI: 10.1126/sciadv.ado5982.

YY1 knockout in pro-B cells impairs lineage commitment, enabling unusual hematopoietic lineage plasticity.

Banerjee S, Sanyal S, Hodawadekar S, Naiyer S, Bano N, Banerjee A Genes Dev. 2024; 38(17-20):887-914.

PMID: 39362773 PMC: 11535188. DOI: 10.1101/gad.351734.124.

The Function of E2A in B-Cell Development.

Miyazaki M, Miyazaki K Adv Exp Med Biol. 2024; 1459:97-113.

PMID: 39017841 DOI: 10.1007/978-3-031-62731-6_5.

References

Chen S, Miyazaki M, Chandra V, Fisch K, Chang A, Murre C . Id3 Orchestrates Germinal Center B Cell Development. Mol Cell Biol. 2016; 36(20):2543-52. PMC: 5038142. DOI: 10.1128/MCB.00150-16. View

Zhang B, Jiao A, Dai M, Wiest D, Zhuang Y . Id3 Restricts γδ NKT Cell Expansion by Controlling Egr2 and c-Myc Activity. J Immunol. 2018; 201(5):1452-1459. PMC: 6103809. DOI: 10.4049/jimmunol.1800106. View

Rivera R, Johns C, Quan J, Johnson R, Murre C . Thymocyte selection is regulated by the helix-loop-helix inhibitor protein, Id3. Immunity. 2000; 12(1):17-26. DOI: 10.1016/s1074-7613(00)80155-7. View

Inlay M, Bhattacharya D, Sahoo D, Serwold T, Seita J, Karsunky H . Ly6d marks the earliest stage of B-cell specification and identifies the branchpoint between B-cell and T-cell development. Genes Dev. 2009; 23(20):2376-81. PMC: 2764492. DOI: 10.1101/gad.1836009. View

Blom B, Heemskerk M, Verschuren M, van Dongen J, Stegmann A, Bakker A . Disruption of alpha beta but not of gamma delta T cell development by overexpression of the helix-loop-helix protein Id3 in committed T cell progenitors. EMBO J. 1999; 18(10):2793-802. PMC: 1171360. DOI: 10.1093/emboj/18.10.2793. View

Wilson A, HELD W, MacDonald H . Two waves of recombinase gene expression in developing thymocytes. J Exp Med. 1994; 179(4):1355-60. PMC: 2191458. DOI: 10.1084/jem.179.4.1355. View

Chien Y, Iwashima M, Wettstein D, Kaplan K, Elliott J, Born W . T-cell receptor delta gene rearrangements in early thymocytes. Nature. 1987; 330(6150):722-7. DOI: 10.1038/330722a0. View

Bories J, Demengeot J, Davidson L, Alt F . Gene-targeted deletion and replacement mutations of the T-cell receptor beta-chain enhancer: the role of enhancer elements in controlling V(D)J recombination accessibility. Proc Natl Acad Sci U S A. 1996; 93(15):7871-6. PMC: 38841. DOI: 10.1073/pnas.93.15.7871. View

Alt F, Yancopoulos G, Blackwell T, Wood C, Thomas E, Boss M . Ordered rearrangement of immunoglobulin heavy chain variable region segments. EMBO J. 1984; 3(6):1209-19. PMC: 557501. DOI: 10.1002/j.1460-2075.1984.tb01955.x. View

10.

Murre C, McCaw P, Vaessin H, Caudy M, Jan L, Jan Y . Interactions between heterologous helix-loop-helix proteins generate complexes that bind specifically to a common DNA sequence. Cell. 1989; 58(3):537-44. DOI: 10.1016/0092-8674(89)90434-0. View

11.

Lauritsen J, Wong G, Lee S, Lefebvre J, Ciofani M, Rhodes M . Marked induction of the helix-loop-helix protein Id3 promotes the gammadelta T cell fate and renders their functional maturation Notch independent. Immunity. 2009; 31(4):565-75. PMC: 2768560. DOI: 10.1016/j.immuni.2009.07.010. View

12.

Sugai M, Gonda H, Kusunoki T, Katakai T, Yokota Y, Shimizu A . Essential role of Id2 in negative regulation of IgE class switching. Nat Immunol. 2002; 4(1):25-30. DOI: 10.1038/ni874. View

13.

Schatz D, Oettinger M, Baltimore D . The V(D)J recombination activating gene, RAG-1. Cell. 1989; 59(6):1035-48. DOI: 10.1016/0092-8674(89)90760-5. View

14.

Shivdasani R, Mayer E, Orkin S . Absence of blood formation in mice lacking the T-cell leukaemia oncoprotein tal-1/SCL. Nature. 1995; 373(6513):432-4. DOI: 10.1038/373432a0. View

15.

Jaleco A, Stegmann A, Heemskerk M, Couwenberg F, Bakker A, Weijer K . Genetic modification of human B-cell development: B-cell development is inhibited by the dominant negative helix loop helix factor Id3. Blood. 1999; 94(8):2637-46. View

16.

Kleiman E, Loguercio S, Feeney A . Epigenetic Enhancer Marks and Transcription Factor Binding Influence Vκ Gene Rearrangement in Pre-B Cells and Pro-B Cells. Front Immunol. 2018; 9:2074. PMC: 6146092. DOI: 10.3389/fimmu.2018.02074. View

17.

Karki S, Kennedy D, McLean K, Grzybowski A, Maienschein-Cline M, Banerjee S . Regulated Capture of Vκ Gene Topologically Associating Domains by Transcription Factories. Cell Rep. 2018; 24(9):2443-2456. PMC: 6310487. DOI: 10.1016/j.celrep.2018.07.091. View

18.

Zhang B, Lin Y, Dai M, Zhuang Y . Id3 and Id2 act as a dual safety mechanism in regulating the development and population size of innate-like γδ T cells. J Immunol. 2014; 192(3):1055-1063. PMC: 3899720. DOI: 10.4049/jimmunol.1302694. View

19.

Bain G, Quong M, Soloff R, Hedrick S, Murre C . Thymocyte maturation is regulated by the activity of the helix-loop-helix protein, E47. J Exp Med. 1999; 190(11):1605-16. PMC: 2195738. DOI: 10.1084/jem.190.11.1605. View

20.

Xiong N, Zhang L, Kang C, Raulet D . Gene placement and competition control T cell receptor gamma variable region gene rearrangement. J Exp Med. 2008; 205(4):929-38. PMC: 2292229. DOI: 10.1084/jem.20071275. View