Changes in replication, nuclear location, and expression of the Igh locus after fusion of a pre-B cell line with a T cell line

Jie Zhou, Shireen Saleque, Olga Ermakova, Manuel A. Sepulveda, Qiaoxin Yang, Laurel A. Eckhardt, Carl L. Schildkraut, Barbara K. Birshtein

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

We have previously observed that replication and nuclear location of the murine Igh locus are developmentally regulated during B cell differentiation. In non-B, B, and plasma cells, sequences near the 3′ end of the Igh locus replicate early in S while upstream Vh sequences replicate late in S, and the Igh locus is located near the nuclear periphery. In fact, in MEL non-B cells, replication of a 500-kb segment containing Igh-C and flanking sequences occurs progressively later throughout S by 3′ to 5′ unidirectional fork movement. In contrast, in pro- and pre-B cells, the entire 3-Mb Igh locus is located away from the nuclear periphery and replicates early in S by forks progressing in both directions. In this study, using an 18-81 (pre-B) × BW5147 (T) cell fusion system in which Igh expression is extinguished, we found that in all Igh alleles, Vh sequences replicated later in S than 3′ Igh sequences (similar to that detected in BW5147), but the Igh locus was situated away from the nuclear periphery (similar to that observed in 18-81). Thus, pre-B cell-derived Igh genes had changes in replication timing, but not in nuclear location, whereas T cell-derived Igh genes changed their nuclear location but not their replication timing. These data are consistent with the silencing of a pre-B cell-specific replication program in the fusion hybrid cells and independent regulation of the nuclear location of Igh loci.

Original languageEnglish (US)
Pages (from-to)2317-2320
Number of pages4
JournalJournal of Immunology
Volume175
Issue number4
DOIs
StatePublished - Aug 15 2005

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology

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