Chromosomal excision of TCRdelta chain genes is dispensable for alphabeta T cell lineage commitment

TCRbeta, delta and gamma chain genes are assembled and expressed in double-negative thymocytes prior to alphabeta or gammadelta T cell lineage commitment. Thus, cells committed to the alphabeta T cell lineage can possess completely assembled TCRdelta and/or TCRgamma chain genes. However, these genes are not expressed. TCRgamma chain gene expression may be silenced through the activity of a cis-acting silencer element. In the TCRalpha/delta locus, the TCRdelta genes lie between the Valpha and Jalpha gene segments, which rearrange by deletion. Moreover, Valpha to Jalpha rearrangements occur on both alleles in essentially all developing alphabeta T cells. Consequently, both TCRdelta chain genes are excised from the chromosome and placed on extrachromosomal circles in mature alphabeta T cells. It has been proposed that this excision process is important for silencing TCRdelta gene expression and permitting alphabeta T cell lineage commitment. A gene-targeting Cre-loxP strategy was used to invert a 75-kb region of the TCRalpha/delta locus encompassing all the Jalpha gene segments, generating the TCRalpha/delta(I) allele. Initial Valpha to Jalpha rearrangements on the TCRalpha/delta(I) allele occur by inversion, resulting in chromosomal retention of TCRdelta chain genes. These TCRdelta chain genes can be productively rearranged and are expressed at levels similar to TCRdelta chain genes in gammadelta T cells. However, alphabeta T cell development appears unperturbed in TCRalpha/delta(I/I) mice. Thus, excision of TCRdelta genes from the chromosome per se is not required for commitment of developing lymphocytes to the alphabeta T cell lineage.     

Pax5对B细胞分化发育调控作用的研究进展

转录因子Pax5在B细胞定向分化发育过程中发挥重要调控作用。B细胞定向分化发育相关的转录因子如PU.1、干扰素调节因子4(Interferon regulatory factor 4,IRF4)、IRF8和NF-κB结合在Pax5基因5’上游增强子区,转录因子EBF、STAT5结合在Pax5基因5’上游启动子区,从而共同促进Pax5基因的表达。表达的Pax5蛋白不仅通过IgH的V(D)J片段染色质的甲基化和乙酰化修饰来调节IgH V(D)J重排,并且通过B细胞特异性基因(mb-1、VpreB、λ5、CD19、BLNK等)表达调控B细胞的定向分化发育。若Pax5基因缺失,影响组蛋白H3-K9的修饰,导致B细胞向非B细胞分化。总之,Pax5在B细胞定向分化发育中起到重要调控作用。     

E2A、EBF和PAX5在早期B细胞分化发育中的作用

早期B细胞分化发育受到各种转录因子调控,特别是转录因子E2A、早期B细胞因子(EBF)及PAX5的调控尤为重要。本文以E2A、EBF与PAX5三个转录因子为综述对象,逐一阐述其在早期B细胞分化发育中的作用,并对3个转录因子在早期B细胞分化发育中的协同作用进行了综述。本文将为"B淋巴细胞分化发育调控机理研究"提供参考。