scholarly journals Expression of a Targeted λ1 Light Chain Gene Is Developmentally Regulated and Independent of Igκ Rearrangements

2003 ◽  
Vol 197 (9) ◽  
pp. 1165-1172 ◽  
Author(s):  
Philipp Oberdoerffer ◽  
Tatiana I. Novobrantseva ◽  
Klaus Rajewsky
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Gene Rearrangement ◽  
Gene Segment ◽  
Chain Gene ◽  
Wild Type ◽  
Immunoglobulin Light Chain ◽  
Developmentally Regulated ◽  
Light Chain Gene

Immunoglobulin light chain (IgL) rearrangements occur more frequently at Igκ than at Igλ. Previous results suggested that the unrearranged Igκ locus negatively regulates Igλ transcription and/or rearrangement. Here, we demonstrate that expression of a VJλ1-joint inserted into its physiological position in the Igλ locus is independent of Igκ rearrangements. Expression of the inserted VJλ1 gene segment is developmentally controlled like that of a VJκ-joint inserted into the Igκ locus and furthermore coincides developmentally with the occurrence of Igκ rearrangements in wild-type mice. We conclude that developmentally controlled transcription of a gene rearrangement in the Igλ locus occurs in the presence of an unrearranged Igκ locus and is therefore not negatively regulated by the latter. Our data also indicate light chain editing in ∼30% of λ1 expressing B cell progenitors.

Ongoing diversification of the rearranged immunoglobulin light-chain gene in a bursal lymphoma cell line

1990 ◽  
Vol 10 (6) ◽  
pp. 3224-3231
Author(s):  
S Kim ◽  
E H Humphries ◽  
L Tjoelker ◽  
L Carlson ◽  
C B Thompson
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Gene Segment ◽  
B Cell Development ◽  
Bursa Of Fabricius ◽  
Chain Gene ◽  
Lymphoma Cell Line ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene

The chicken immunoglobulin light-chain gene (IgL) encodes only a single variable gene segment capable of recombination. To generate an immune repertoire, chickens diversify this unique rearranged VL gene segment during B-cell development in the bursa of Fabricius. Sequence analysis of IgL cDNAs suggests that both gene conversion events derived from VL segment pseudogene templates (psi VL) and non-template-derived single-base-pair substitutions contribute to this diversity. To facilitate the study of postrecombinational mechanisms of immunoglobulin gene diversification, avian B-cell lines were examined for the ability to diversify their rearranged IgL gene during in vitro passage. One line that retains this ability, the avian leukosis virus-induced bursal lymphoma cell line DT40, has been identified. After passage for 1 year in culture, 39 of 51 randomly sequenced rearranged V-J segments from a DT40 population defined novel subclones of the parental tumor. All cloned V-J segments displayed the same V-J joint, confirming that the observed diversity arose after V-J rearrangement. Most sequence variations that we observed (203 of 220 base pairs) appeared to result from psi VL-derived gene conversion events; 16 of the 17 novel single nucleotide substitutions were transitions. Based on these data, it appears that immunoglobulin diversification during in vitro passage of DT40 cells is representative of the diversification that occurs during normal B-cell development in the bursa of Fabricius.

scholarly journals Ongoing diversification of the rearranged immunoglobulin light-chain gene in a bursal lymphoma cell line.

1990 ◽  
Vol 10 (6) ◽  
pp. 3224-3231 ◽  
Author(s):  
S Kim ◽  
E H Humphries ◽  
L Tjoelker ◽  
L Carlson ◽  
C B Thompson
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Gene Segment ◽  
B Cell Development ◽  
Bursa Of Fabricius ◽  
Chain Gene ◽  
Lymphoma Cell Line ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene

The chicken immunoglobulin light-chain gene (IgL) encodes only a single variable gene segment capable of recombination. To generate an immune repertoire, chickens diversify this unique rearranged VL gene segment during B-cell development in the bursa of Fabricius. Sequence analysis of IgL cDNAs suggests that both gene conversion events derived from VL segment pseudogene templates (psi VL) and non-template-derived single-base-pair substitutions contribute to this diversity. To facilitate the study of postrecombinational mechanisms of immunoglobulin gene diversification, avian B-cell lines were examined for the ability to diversify their rearranged IgL gene during in vitro passage. One line that retains this ability, the avian leukosis virus-induced bursal lymphoma cell line DT40, has been identified. After passage for 1 year in culture, 39 of 51 randomly sequenced rearranged V-J segments from a DT40 population defined novel subclones of the parental tumor. All cloned V-J segments displayed the same V-J joint, confirming that the observed diversity arose after V-J rearrangement. Most sequence variations that we observed (203 of 220 base pairs) appeared to result from psi VL-derived gene conversion events; 16 of the 17 novel single nucleotide substitutions were transitions. Based on these data, it appears that immunoglobulin diversification during in vitro passage of DT40 cells is representative of the diversification that occurs during normal B-cell development in the bursa of Fabricius.

scholarly journals Rearrangement and Expression of Immunoglobulin Light Chain Genes Can Precede Heavy Chain Expression during Normal B Cell Development in Mice

1999 ◽  
Vol 189 (1) ◽  
pp. 75-88 ◽  
Author(s):  
Tatiana I. Novobrantseva ◽  
Verena M. Martin ◽  
Roberta Pelanda ◽  
Werner Müller ◽  
Klaus Rajewsky ◽  
...  
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Single Cell Analysis ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
Cell Analysis ◽  
Wild Type ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene ◽  
Mouse Mutants

In mouse mutants incapable of expressing μ chains, VκJκ joints are detected in the CD43+ B cell progenitors. In agreement with these earlier results, we show by a molecular single cell analysis that 4–7% of CD43+ B cell progenitors in wild-type mice rearrange immunoglobulin (Ig)κ genes before the assembly of a productive VHDHJH joint. Thus, μ chain expression is not a prerequisite to Igκ light chain gene rearrangements in normal development. Overall, ∼15% of the total CD43+ B cell progenitor population carry Igκ gene rearrangements in wild-type mice. Together with the results obtained in the mouse mutants, these data fit a model in which CD43+ progenitors rearrange IgH and Igκ loci independently, with a seven times higher frequency in the former. In addition, we show that in B cell progenitors VκJκ joining rapidly initiates κ chain expression, irrespective of the presence of a μ chain.

scholarly journals ImmunoglobulinλGene Rearrangement Can PrecedeκGene Rearrangement

1990 ◽  
Vol 1 (1) ◽  
pp. 53-57 ◽  
Author(s):  
Jörg Berg ◽  
Mindy Mcdowell ◽  
Hans-Martin Jäck ◽  
Matthias Wabl
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Light Chain ◽  
Gene Rearrangement ◽  
Germ Line ◽  
Stochastic Theory ◽  
Chain Gene ◽  
Light Chain Gene ◽  
Line Configuration ◽  
Chain Gene Rearrangement

Immunoglobulin genes are generated during differentiation of B lymphocytes by joining gene segments. A mouse pre-B cell contains a functional immunoglobulin heavy-chain gene, but no light-chain gene. Although there is only one heavy-chain locus, there are two lightchain loci:κandλ.It has been reported thatκloci in the germ-line configuration are never (in man) or very rarely (in the mouse) present in cells with functionally rearrangedλ-chain genes. Two explanations have been proposed to explain this: (a) the ordered rearrangement theory, which postulates that light-chain gene rearrangement in the pre-B cell is first attempted at theκlocus, and that only upon failure to produce a functionalκchain is there an attempt to rearrange theλlocus; and (b) the stochastic theory, which postulates that rearrangement at theλlocus proceeds at a rate that is intrinsically much slower than that at theκlocus. We show here thatλ-chain genes are generated whether or not theκlocus has lost its germ-line arrangement, a result that is compatible only with the stochastic theory.

scholarly journals Immunoglobulin x light chain gene promoter and enhancer are not responsible for B-cell restricted gene rearrangement

1989 ◽  
Vol 17 (18) ◽  
pp. 7403-7415 ◽  
Author(s):  
Michele Goodhardt ◽  
Charles Babinet ◽  
Georges Lutfalla ◽  
Sacha Kallenbach ◽  
Patricia Caveher ◽  
...  
Keyword(s):  
B Cell ◽  
Light Chain ◽  
Gene Rearrangement ◽  
Gene Promoter ◽  
Chain Gene ◽  
Light Chain Gene

scholarly journals Bruton’s Tyrosine Kinase and SLP-65 Regulate Pre-B Cell Differentiation and the Induction of Ig Light Chain Gene Rearrangement

2006 ◽  
Vol 176 (8) ◽  
pp. 4543-4552 ◽  
Author(s):  
Rogier Kersseboom ◽  
Van B. T. Ta ◽  
A. J. Esther Zijlstra ◽  
Sabine Middendorp ◽  
Hassan Jumaa ◽  
...  
Keyword(s):  
Cell Differentiation ◽  
Tyrosine Kinase ◽  
B Cell ◽  
Light Chain ◽  
Gene Rearrangement ◽  
Chain Gene ◽  
B Cell Differentiation ◽  
Bruton's Tyrosine Kinase ◽  
Light Chain Gene ◽  
Chain Gene Rearrangement
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