Cytidine deaminase 2 is required for VLRB antibody gene assembly in lampreys

2020 ◽  
Vol 5 (45) ◽  
pp. eaba0925 ◽  
Author(s):  
Ryo Morimoto ◽  
Connor P. O’Meara ◽  
Stephen J. Holland ◽  
Inês Trancoso ◽  
Ahmed Souissi ◽  
...  
Keyword(s):  
B Lymphocyte ◽  
Cytidine Deaminase ◽  
Receptor Gene ◽  
Cell Lineage ◽  
Antigen Receptor ◽  
Immunoglobulin Gene ◽  
Gene Assembly ◽  
Lampetra Planeri ◽  
B Lymphocyte Development ◽  
Somatic Diversification

The antibodies of jawless vertebrates consist of leucine-rich repeat arrays encoded by somatically assembled VLRB genes. It is unknown how the incomplete germline VLRB loci are converted into functional antibody genes during B lymphocyte development in lampreys. In Lampetra planeri larvae lacking the cytidine deaminase CDA2 gene, VLRB assembly fails, whereas the T lineage–associated VLRA and VLRC antigen receptor gene assemblies occur normally. Thus, CDA2 acts in a B cell lineage–specific fashion to support the somatic diversification of VLRB antibody genes. CDA2 is closely related to activation-induced cytidine deaminase (AID), which is essential for the elaboration of immunoglobulin gene repertoires in jawed vertebrates. Our results thus identify a convergent mechanism of antigen receptor gene assembly and diversification that independently evolved in the two sister branches of vertebrates.

Diagnosis of Canine Lymphoid Neoplasia Using Clonal Rearrangements of Antigen Receptor Genes

2003 ◽  
Vol 40 (1) ◽  
pp. 32-41 ◽  
Author(s):  
R. C. Burnett ◽  
W. Vernau ◽  
J. F. Modiano ◽  
C. S. Olver ◽  
P. F. Moore ◽  
...  
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Gene Rearrangement ◽  
Receptor Gene ◽  
Antigen Receptor ◽  
Cell Receptor ◽  
Immunoglobulin Gene ◽  
Lymphoid Malignancy ◽  
Variable Regions ◽  
Lymphoid Neoplasia

Although the diagnosis of canine leukemia and lymphoma in advanced stages is usually uncomplicated, some presentations of the disease can be a diagnostic challenge. In certain situations, lymphoma and leukemia can be difficult to distinguish from a benign reactive proliferation of lymphocytes. Because clonality is the hallmark of malignancy, we have developed an assay that uses the polymerase chain reaction to amplify the variable regions of immunoglobulin genes and T-cell receptor genes to detect the presence of a clonal lymphocyte population. The assay detected clonally rearranged antigen receptor genes in 91% of the 77 dogs with lymphoid malignancy. Of the 24 dogs tested, that were either healthy or had clearly defined conditions not related to lymphoid malignancy, a clonally rearranged antigen receptor gene was found in one (a dog with Ehrlichia canis infection). Gene rearrangement was appropriate for the immunophenotype (immunoglobulin gene rearrangement in B-cell leukemias and T-cell receptor gene rearrangement in T-cell leukemias). Dilution analysis showed that the clonal rearrangement could be detected when 0.1–10% of the DNA was derived from neoplastic cells, depending on the source tissue. Potential applications of this assay include the diagnosis of lymphoma or leukemia in biopsy samples, cavity fluids, fine needle aspirates, bone marrow and peripheral blood; the determination of lineage (B or T cell); staging of lymphoma; and detection of residual disease after chemotherapy.

A new antigen receptor gene family that undergoes rearrangement and extensive somatic diversification in sharks

Nature ◽  
1995 ◽  
Vol 374 (6518) ◽  
pp. 168-173 ◽  
Author(s):  
Andrew S. Greenberg ◽  
David Avila ◽  
Marianne Hughes ◽  
Austin Hughes ◽  
E. Churchill McKinney ◽  
...  
Keyword(s):  
Gene Family ◽  
Receptor Gene ◽  
Antigen Receptor ◽  
Somatic Diversification ◽  
Receptor Gene Family

scholarly journals Evidence for peripheral blood B lymphocyte but not T lymphocyte involvement in multiple myeloma

Blood ◽  
1987 ◽  
Vol 70 (5) ◽  
pp. 1550-1553 ◽  
Author(s):  
J Berenson ◽  
R Wong ◽  
K Kim ◽  
N Brown ◽  
A Lichtenstein
Keyword(s):  
Multiple Myeloma ◽  
T Cell ◽  
T Cell Receptor ◽  
Peripheral Blood ◽  
B Lymphocyte ◽  
Plasma Cells ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Peripheral Blood Lymphocytes ◽  
Immunoglobulin Gene

Because there is controversy regarding whether subsets of peripheral blood lymphocytes (PBLs) are part of the malignant clone in patients with multiple myeloma, we studied this question by immunoglobulin and T cell receptor gene analysis. Southern blot analysis with antibody probes demonstrated clonal immunoglobulin gene rearrangements in PBLs of seven of nine patients that were identical to those seen in their marrow plasma cells. Circulating plasma cells were not detected in any of these patients. In contrast, no patient demonstrated clonally rearranged T cell receptor genes. In one sequentially studied patient, PBLs obtained at diagnosis when he had stage I (Durie-Salmon) contained only germline DNA, while analysis of PBLs at relapse (stage III) revealed a clonally rearranged band. These data confirm the notion that circulating lymphocytes in patients with myeloma are part of the malignant clone and, furthermore, these malignant cells are of B cell rather than T cell lineage.

scholarly journals The structure of the T cell antigen receptor genes in normal and malignant T cells

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 327-336
Author(s):  
MD Minden ◽  
TW Mak
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lineage ◽  
Antigen Receptor ◽  
Immunoglobulin Gene ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Alpha Chain ◽  
T Cell Malignancies

In this review the genomic structure and the RNA transcripts of the alpha and beta chain of the T cell antigen receptor have been discussed. Studies of the structure of TcR beta in hematologic malignancies have revealed rearrangement in almost all of the T cell malignancies and a small proportion of non-T cell malignancies. In addition, clonal involvement of T cells in diseases such as Hodgkin's disease, angioimmunoblastic lymphadenopathy, and chronic T cell lymphocytosis have been observed. The study of the structure of the TcR beta gene is thus a useful tool for identifying clonal expansions of cells and in conjunction with studies of the immunoglobulin gene structure, and cell surface markers a useful tool for identifying cell lineage. At the present time the evaluation of the structure of the alpha chain genes has not been as fruitful. However, chromosome translocations involving the TcR alpha chain genes have been recognized and, in one case, this rearrangement has been in association with a known oncogene. With the isolation of more probes to the alpha chain region it should be possible to test its utility in identifying clonal populations and cell lineage. The recent isolation of the gamma gene of the T cell will also permit such studies. Preliminary results of studies carried out with a probe to the gamma chain gene of the T cell have paralleled results obtained with the TcR beta probe (unpublished observation).

scholarly journals Breaking down cell cycle checkpoints and DNA repair during antigen receptor gene assembly

Oncogene ◽  
2007 ◽  
Vol 26 (56) ◽  
pp. 7759-7764 ◽  
Author(s):  
E Callén ◽  
M C Nussenzweig ◽  
A Nussenzweig
Keyword(s):  
Cell Cycle ◽  
Dna Repair ◽  
Receptor Gene ◽  
Antigen Receptor ◽  
Cell Cycle Checkpoints ◽  
Gene Assembly

Regulating antigen-receptor gene assembly

2003 ◽  
Vol 3 (11) ◽  
pp. 890-899 ◽  
Author(s):  
Mark S. Schlissel
Keyword(s):  
Receptor Gene ◽  
Antigen Receptor ◽  
Gene Assembly

scholarly journals The structure of the T cell antigen receptor genes in normal and malignant T cells

Blood ◽  
1986 ◽  
Vol 68 (2) ◽  
pp. 327-336 ◽  
Author(s):  
MD Minden ◽  
TW Mak
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cell Lineage ◽  
Antigen Receptor ◽  
Immunoglobulin Gene ◽  
T Cell Antigen Receptor ◽  
Cell Antigen Receptor ◽  
Cell Antigen ◽  
Alpha Chain ◽  
T Cell Malignancies

Abstract In this review the genomic structure and the RNA transcripts of the alpha and beta chain of the T cell antigen receptor have been discussed. Studies of the structure of TcR beta in hematologic malignancies have revealed rearrangement in almost all of the T cell malignancies and a small proportion of non-T cell malignancies. In addition, clonal involvement of T cells in diseases such as Hodgkin's disease, angioimmunoblastic lymphadenopathy, and chronic T cell lymphocytosis have been observed. The study of the structure of the TcR beta gene is thus a useful tool for identifying clonal expansions of cells and in conjunction with studies of the immunoglobulin gene structure, and cell surface markers a useful tool for identifying cell lineage. At the present time the evaluation of the structure of the alpha chain genes has not been as fruitful. However, chromosome translocations involving the TcR alpha chain genes have been recognized and, in one case, this rearrangement has been in association with a known oncogene. With the isolation of more probes to the alpha chain region it should be possible to test its utility in identifying clonal populations and cell lineage. The recent isolation of the gamma gene of the T cell will also permit such studies. Preliminary results of studies carried out with a probe to the gamma chain gene of the T cell have paralleled results obtained with the TcR beta probe (unpublished observation).

scholarly journals Genome Topology Control of Antigen Receptor Gene Assembly

2020 ◽  
Vol 204 (10) ◽  
pp. 2617-2626 ◽  
Author(s):  
Brittney M. Allyn ◽  
Kyutae D. Lee ◽  
Craig H. Bassing
Keyword(s):  
Topology Control ◽  
Receptor Gene ◽  
Antigen Receptor ◽  
Gene Assembly

Lymphocyte Antigen Receptor Gene Assembly: Multiple Layers of Regulation

2005 ◽  
Vol 32 (1-3) ◽  
pp. 253-258 ◽  
Author(s):  
Barry P. Sleckman
Keyword(s):  
Receptor Gene ◽  
Antigen Receptor ◽  
Gene Assembly ◽  
Lymphocyte Antigen

Regulation of Antigen Receptor Gene Assembly In Lymphocytes

2001 ◽  
Vol 23 (2-3) ◽  
pp. 121-134 ◽  
Author(s):  
Eugene M Oltz
Keyword(s):  
Receptor Gene ◽  
Antigen Receptor ◽  
Gene Assembly
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