1/31/2024 0 Comments Lineage w ruDN cells progress through stages of DN1 through DN4. Most highly immature progenitors, comprising about 1–2% of thymocytes, are double-negative (DN) cells that express neither CD4 nor CD8. Ik1 is responsible for the differentiation and/or survival of a common lymphoid progenitor and is defined as the earliest transcriptional checkpoint in lymphoid lineage commitment (Ref. The earliest stages of T-cell lineage commitment also witness expression of two transcription factors, Ik1 and GATA3 (GATA Binding Protein-3). Once the cells stop expressing c-Kit and markedly reduce CD44 expression, they begin to rearrange their TCR genes. During this period, the cells proliferate but the TCR genes remain unrearranged. The initial thymocyte population displays c-Kit, the receptor for stem cell growth factor, and subsequently expresses CD44, an adhesion molecule, and then CD25, the Alpha-Chain of the IL-2 Receptor. 2).Įven though these co-receptors are not expressed in the early phase, the expression of other cell surface molecules, particularly the THY1 (Thy1 T-Cell Antigen), c-Kit, CD44 (CD44 Antigen) and CD25 (CD25 Antigen), marks the developmental progression of the DN (Double Negative) population. The mistake-prone instruction of lineage choice precedes a subsequent selection step that filters out most incorrect decisions (Ref. Two models are proposed initially to explain the remarkable outcome-‘instruction’ of lineage choice by initial signaling events or ‘selection’ after a stochastic fate decision which limits further development to cells with coordinated TCR and co-receptor specificities. Each mature T-cell generally retains expression of the co-receptor molecule (CD4 or CD8) that has an MHC (Major Histocompatibility Complex)-binding property that matches that of its TCR (Ref. Therefore, the lineage-specific differentiation of immature CD4+CD8+ (CD4 Antigen Positive CD8 Antigen Positive) T-cells into CD4+ or CD8+ mature T-cells is regulated by clonally-expressed, somatically-generated TCRs (T-Cell Receptors) of unpredictable fine specificity. These clonal receptors help to determine which precursor lymphocytes will successfully mature. But, adaptive immunity depends on the function of T- and B-cells, which express unique surface receptors that are created by somatic DNA rearrangement and random chain pairing. Signals from broadly expressed receptors that interact with co-evolved germline ligands control most differentiation decisions. The physiological function of a multicellular organism depends on the generation of the proper number and diversity of cell types.
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