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B cells are programmed to activate κ and λ for rearrangement at consecutive developmental stages

✍ Scribed by Holger Engel; Antonius Rolink; Siegfried Weiss


Publisher
John Wiley and Sons
Year
1999
Tongue
English
Weight
174 KB
Volume
29
Category
Article
ISSN
0014-2980

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✦ Synopsis


O and Q , the two types of immunoglobulin light (L) chains present in mammals, contribute differently to the L chain pool of each species. Here we show that the extreme preponderance of O in the mouse results from programmed sequential activation of the O and Q loci. Activation -a prerequisite of rearrangement -was monitored by analyzing transcription of unrearranged J-C clusters. Upon in vitro differentiation of a rearrangement-deficient pro/pre-B line, germ-line transcripts of the Q J-C clusters, that are newly described here, became detectable 2 days later than their counterparts of J-C O . Clear differences could also be observed in vivo: germ-line transcripts of O were already present in large B220 + CD25 + pre B-II cells whereas germ-line Q transcripts first became detectable at the consecutive developmental stage of small B220 + CD25 + pre-B-II cells. This activation pattern was found to be identical in mice which can not rearrange O due to a targeted deletion or inactivation of O . This suggests that pre-B-II cells follow a hit-and-run mechanism of development which includes programmed transitions and differential activation of the L chain loci, i. e. O first, then Q . Thus, privileged activation of O might be the decisive factor in setting the 10:1 ratio of O to Q present in the mouse.