The E-Id axis specifies adaptive and innate lymphoid lineage cell fates

Our bodies are constantly threatened with the invasion of pathogens, such as bacteria and virus. Immune responses against pathogens are evoked in collaboration with adaptive and innate immune systems. Adaptive immune cells including T and B cells recognize various antigens from pathogens through the antigen recognition receptors such as immunoglobulin (Ig) and T-cell receptor (TCR), and they evoke antigen-specific immune responses to eliminate the pathogens. This specific recognition of a variety of antigens relies on the V(D)J DNA recombination of Ig and TCR genes, which is generated by the Rag (recombination activation gene) 1/Rag2 protein complex. The expression of Rag1/2 genes is stringently controlled during the T and B cell development; Rag1/2 gene expression indicates the commitment towards adaptive lymphocyte lineages. In this review article, we will discuss the developmental bifurcation between adaptive and innate lymphoid cells, and the role of transcription factors, especially the E and Id proteins, upon the lineage commitment, and the regulation of Rag gene locus.