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Stimulation of κ Light-Chain Gene Rearrangement by the Immunoglobulin, µ Heavy Chain in a Pre-B-Cell Line

Shapiro, Alan M. and Schlissel, Mark S. and Baltimore, David and DeFranco, Anthony L. (1993) Stimulation of κ Light-Chain Gene Rearrangement by the Immunoglobulin, µ Heavy Chain in a Pre-B-Cell Line. Molecular and Cellular Biology, 13 (9). pp. 5679-5690. ISSN 0270-7306. http://resolver.caltech.edu/CaltechAUTHORS:20120308-110917005

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Abstract

B-lymphocyte development exhibits a characteristic order of immunoglobulin gene rearrangements. Previous work has led to the hypothesis that expression of the immunoglobulin µ heavy chain induces rearrangement activity at the K light-chain locus. To examine this issue in more detail, we isolated five matched pairs of µ^- and endogenously rearranged µ^+ cell lines from the Abelson murine leukemia virus-transformed pro-B-cell line K.40. In four of the five µ^+ cell lines, substantial expression of µ protein on the cell surface was observed, and this correlated with an enhanced frequency of K immunoglobulin gene rearrangement compared with that in the matched µ^- cell lines. This increased K gene rearrangement frequency was not due to a general increase in the amount of V(D)J recombinase activity in the µ^+ cells. Consistently, introduction of a functionally rearranged µ gene into one of the µ^- pre-B-cell lines resulted in a fivefold increase in K gene rearrangements. In three of the four clonally matched pairs with increased K gene rearrangements, the increase in rearrangement frequency was not accompanied by a significant increase in germ line transcripts from the C_K locus. However, in the fourth pair, K.40D, we observed an increase in germ line transcription of the kappa locus after expression of µ protein encoded by either an endogenously rearranged or a transfected functional heavy-chain allele. In these cells, the amount of the germ line C_K transcript correlated with the measured frequency of rearranged K genes. These results support a regulated model of B-cell development in which µ protein expression in some way targets the V(D)J recombinase to the K gene locus.


Item Type:Article
Related URLs:
URLURL TypeDescription
http://dx.doi.org/10.1128/MCB.13.9.5679DOIUNSPECIFIED
http://mcb.asm.org/content/13/9/5679PublisherUNSPECIFIED
Additional Information:© 1993 American Society for Microbiology. Received 29 February 1993. Returned for modification 18 May 1993. Accepted 22 June 1993. We thank M. Wabl for providing the cell line K.40 as well as advice; D. Littman for use of his FACScan and for advice; A. Weiss for advice; R. Stafford for his help with statistics; and H.-M. Jack, M. Lieber, and P. Mittelstadt for technical advice. We are also grateful to V. Chan, M. Crowley, J. Hambleton, S. Harmer, M. Home, D. Law, J. Richards, T. Stevens, and S. Weinstein for critical reading of all or part of the manuscript. A.M.S. is a trainee in the Medical Scientist Program at UCSF and has been supported by NIGMS MSTP UCSF grant GM07618, the Sussman Fund, the Gordon Tomkins Memorial Fund, and a California Universitywide AIDS Research grant. M.S.S. acknowledges the support of a Cancer Research Institute investigator award. This work was supported by the Simon Fund, School of Medicine, UCSF; funds from the Academic Senate, UCSF; and a grant from the Cancer Research Coordinating Committee of the University of California.
Funders:
Funding AgencyGrant Number
NIGMS MSTP UCSFGM07618
Sussman FundUNSPECIFIED
Gordon Tomkins Memorial FundUNSPECIFIED
California Universitywide AIDS Research grantUNSPECIFIED
Cancer Research Institute UNSPECIFIED
UCSF School of Medicine Simon FundUNSPECIFIED
UCSF Academic SenateUNSPECIFIED
University of California Cancer Coordinating CommitteeUNSPECIFIED
Record Number:CaltechAUTHORS:20120308-110917005
Persistent URL:http://resolver.caltech.edu/CaltechAUTHORS:20120308-110917005
Official Citation:Stimulation of K light-chain gene rearrangement by the immunoglobulin µ heavy chain in a pre-B-cell line. A M Shapiro, M S Schlissel, D Baltimore, and A L DeFranco Mol. Cell. Biol. September 1993 13:5679-5690; doi:10.1128/MCB.13.9.5679
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:29650
Collection:CaltechAUTHORS
Deposited By: Ruth Sustaita
Deposited On:12 Mar 2012 20:20
Last Modified:12 Mar 2012 20:20

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