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 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.

Rearrangement and diversification of immunoglobulin light-chain genes in lymphoid cells transformed by reticuloendotheliosis virus

1989 ◽  
Vol 9 (11) ◽  
pp. 4970-4976
Author(s):  
J Y Zhang ◽  
W Bargmann ◽  
H R Bose
Keyword(s):  
Cell Lines ◽  
Light Chain ◽  
Lymphoid Cells ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
B Cell Differentiation ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene ◽  
Transformed Cell Lines

Avian lymphoid cells transformed by reticuloendotheliosis virus (REV-T) serve as a model to analyze the mechanism by which B-cell differentiation and antibody diversification occur in birds. Immunoglobulin light-chain gene rearrangements, diversification, and expression were analyzed in 72 independently derived REV-T-transformed cell lines. Lymphoid cells transformed as the result of expression of the v-rel oncogene were divided into two distinct groups based on light-chain gene rearrangements. The status of the light-chain gene loci in these REV-T-transformed cell lines was determined in part by the ages of the chickens whose spleen cells were transformed. In embryonic spleen cell lines transformed by the v-rel oncogene, rearrangements were not detected, even after prolonged culture in vitro, indicating that these cells are arrested in B-cell differentiation. REV-T transformants derived from spleens obtained from chickens 2 weeks old or older, however, had at least one light-chain allele rearranged. All of the cell lines analyzed which exhibited rearranged light-chain genes contained light-chain transcripts, and most of the REV-T-transformed cells which displayed light-chain rearrangements expressed immunoglobulin protein. REV-T, therefore, transforms B-lymphoid cells at phenotypically different stages of development. Many REV-T-transformed cells undergo immunoglobulin chain gene rearrangements during prolonged propagation in vitro. Most of the cell lines which rearrange their light-chain alleles also undergo diversification during cultivation in vitro. Light-chain diversification occurs during or after the rearrangement event.

scholarly journals Rearrangement and diversification of immunoglobulin light-chain genes in lymphoid cells transformed by reticuloendotheliosis virus.

1989 ◽  
Vol 9 (11) ◽  
pp. 4970-4976 ◽  
Author(s):  
J Y Zhang ◽  
W Bargmann ◽  
H R Bose
Keyword(s):  
Cell Lines ◽  
Light Chain ◽  
Lymphoid Cells ◽  
Chain Gene ◽  
Gene Rearrangements ◽  
B Cell Differentiation ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene ◽  
Transformed Cell Lines

Avian lymphoid cells transformed by reticuloendotheliosis virus (REV-T) serve as a model to analyze the mechanism by which B-cell differentiation and antibody diversification occur in birds. Immunoglobulin light-chain gene rearrangements, diversification, and expression were analyzed in 72 independently derived REV-T-transformed cell lines. Lymphoid cells transformed as the result of expression of the v-rel oncogene were divided into two distinct groups based on light-chain gene rearrangements. The status of the light-chain gene loci in these REV-T-transformed cell lines was determined in part by the ages of the chickens whose spleen cells were transformed. In embryonic spleen cell lines transformed by the v-rel oncogene, rearrangements were not detected, even after prolonged culture in vitro, indicating that these cells are arrested in B-cell differentiation. REV-T transformants derived from spleens obtained from chickens 2 weeks old or older, however, had at least one light-chain allele rearranged. All of the cell lines analyzed which exhibited rearranged light-chain genes contained light-chain transcripts, and most of the REV-T-transformed cells which displayed light-chain rearrangements expressed immunoglobulin protein. REV-T, therefore, transforms B-lymphoid cells at phenotypically different stages of development. Many REV-T-transformed cells undergo immunoglobulin chain gene rearrangements during prolonged propagation in vitro. Most of the cell lines which rearrange their light-chain alleles also undergo diversification during cultivation in vitro. Light-chain diversification occurs during or after the rearrangement event.

scholarly journals Phospholipase Cγ2 Contributes to Light-Chain Gene Activation and Receptor Editing

2007 ◽  
Vol 27 (17) ◽  
pp. 5957-5967 ◽  
Author(s):  
Li Bai ◽  
Yuhong Chen ◽  
Yinghong He ◽  
Xuezhi Dai ◽  
Xueyan Lin ◽  
...  
Keyword(s):  
B Cells ◽  
B Cell ◽  
Light Chain ◽  
Gene Activation ◽  
Chain Gene ◽  
Receptor Editing ◽  
Light Chain Gene ◽  
Transitional Type

ABSTRACT Phospholipase Cγ2 (PLCγ2) is critical for pre-B-cell receptor (pre-BCR) and BCR signaling. Current studies discovered that PLCγ2-deficient mice had reduced immunoglobulin λ (Igλ) light-chain usage throughout B-cell maturation stages, including transitional type 1 (T1), transitional type 2 (T2), and mature follicular B cells. The reduction of Igλ rearrangement by PLCγ2 deficiency was not due to specifically increased apoptosis or decreased proliferation of mutant Igλ+ B cells, as lack of PLCγ2 exerted a similar effect on apoptosis and proliferation of both Igλ+ and Igκ+ B cells. Moreover, PLCγ2-deficient IgHEL transgenic B cells exhibited an impairment of antigen-induced receptor editing among both the endogenous λ and κ loci in vitro and in vivo. Importantly, PLCγ2 deficiency impaired BCR-induced expression of IRF-4 and IRF-8, the two transcription factors critical for λ and κ light-chain rearrangements. Taken together, these data demonstrate that the PLCγ2 signaling pathway plays a role in activation of light-chain loci and contributes to receptor editing.

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 Preferential linkage of bcl-2 to immunoglobulin light chain gene in chronic lymphocytic leukemia.

1990 ◽  
Vol 171 (2) ◽  
pp. 559-564 ◽  
Author(s):  
M Adachi ◽  
A Tefferi ◽  
P R Greipp ◽  
T J Kipps ◽  
Y Tsujimoto
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Light Chain ◽  
Chromosome Translocation ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Immunoglobulin Light Chain ◽  
Light Chain Gene ◽  
Flanking Region ◽  
Follicular Lymphomas

Most of human follicular lymphomas possess the t(14;18) chromosome translocation that juxtaposes the IgH gene to the 3' region of bcl-2 in a head-to-tail configuration. Here we show that the rearrangement of the bcl-2 gene occurs in a significant fraction (approximately of 10%) of B cell CLL. In all cases analyzed, breakpoints on chromosome 18 clustered at the 5' flanking region of the bcl-2 gene, and no rearrangements were found at the major or minor breakpoint clustering region (3' region of bcl-2 gene) typical of the t(14;18) chromosome translocation. All of the rearranged bcl-2 genes were juxtaposed with the Ig lambda or K genes in a head-to-head configuration. These results imply that the bcl-2 gene is preferentially linked to the IgL genes in CLL and could function in leukemogenesis.

Sign in / Sign up

Export Citation Format

Share Document