title: B cells are programmed to activate kappa and lambda for rearrangement at consecutive developmental stages.
abstract: Kappa and lambda, 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 kappa in the mouse results from programmed sequential activation of the kappa and lambda 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 lambda J-C clusters, that are newly described here, became detectable 2 days later than their counterparts of J-C kappa. Clear differences could also be observed in vivo: germ-line transcripts of kappa were already present in large B220+ CD25+ pre B-II cells whereas germ-line lambda 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 kappa due to a targeted deletion or inactivation of kappa. 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. kappa first, then lambda. Thus, privileged activation of kappa might be the decisive factor in setting the 10:1 ratio of kappa to lambda present in the mouse.
authors.affiliation: Molecular Immunology, GBF, National Research Center for Biotechnology, Braunschweig, Germany. hen@gbf.de
authors.forename: H
authors.initials: H
authors.lastname: Engel
authors.forename: A
authors.initials: A
authors.lastname: Rolink
authors.forename: S
authors.initials: S
authors.lastname: Weiss
mesh_terms: D000818:Animals; D001402:B-Lymphocytes / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D001483:Base Sequence; D002454:Cell Differentiation; D002460:Cell Line; D003001:Cloning, Molecular; D004247:DNA / Q000235:genetics; D017931:DNA Primers / Q000235:genetics; D005786:Gene Expression Regulation; D015328:Gene Rearrangement, B-Lymphocyte, Light Chain; D005854:Germ Cells / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D008969:Molecular Sequence Data; D012313:RNA / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D012313:RNA; D004247:DNA