Generation of the primary antibody repertoire in rabbits: expression of a diverse set of Igk-V genes may compensate for limited combinatorial diversity at the heavy chain locus

1999 ◽  
Vol 50 (1-2) ◽  
pp. 31-42 ◽  
Author(s):  
Devinder Sehgal ◽  
George Johnson ◽  
Tai T. Wu ◽  
R. G. Mage
Keyword(s):  
Heavy Chain ◽  
Primary Antibody ◽  
Antibody Repertoire ◽  
Chain Locus ◽  
Heavy Chain Locus ◽  
V Genes

scholarly journals Inversions produced during V(D)J rearrangement at IgH, the immunoglobulin heavy-chain locus.

1995 ◽  
Vol 15 (2) ◽  
pp. 671-681 ◽  
Author(s):  
A E Sollbach ◽  
G E Wu
Keyword(s):  
Heavy Chain ◽  
Adult Mouse ◽  
Fetal Liver ◽  
Immunoglobulin Heavy Chain ◽  
Antigen Receptors ◽  
Adult Mice ◽  
Chain Locus ◽  
Heavy Chain Locus ◽  
Fetal Liver Cells

Diversity in immunoglobulin antigen receptors is generated in part by V(D)J recombination. In this process, different combinations of gene elements are joined in various configurations. Products of V(D)J recombination are coding joints, signal joints, and hybrid junctions, which are generated by deletion or inversion. To determine their role in the generation of diversity, we have examined two sorts of recombination products, coding joints and hybrid junctions, that have formed by inversion at the mouse immunoglobulin heavy-chain locus. We developed a PCR assay for quantification and characterization of inverted rearrangements of DH and JH gene elements. In primary cells from adult mice, inverted DJH rearrangements are detectable but they are rare. There were approximately 1,100 to 2,200 inverted DJH coding joints and inverted DJH hybrid junctions in the marrow of one adult mouse femur. On day 16 of gestation, inverted DJH rearrangements are more abundant. There are approximately 20,000 inverted DJH coding joints and inverted DJH hybrid junctions per day 16 fetal liver. In fetal liver cells, the number of inverted DJH rearrangements remains relatively constant from day 14 to day 16 of gestation. Inverted DJH rearrangements to JH4, the most 3' JH element, are more frequently detected than inverted DJH rearrangements to other JH elements. We compare the frequencies of inverted DJH rearrangements to previously determined frequencies of uninverted DJH rearrangements (DJH rearrangements formed by deletion). We suggest that inverted DJH rearrangements are influenced by V(D)J recombination mechanistic constraints and cellular selection.

scholarly journals The enhancer of the immunoglobulin heavy chain locus is flanked by presumptive chromosomal loop anchorage elements.

1987 ◽  
Vol 262 (11) ◽  
pp. 5394-5397
Author(s):  
P.N. Cockerill ◽  
M.H. Yuen ◽  
W.T. Garrard
Keyword(s):  
Heavy Chain ◽  
Immunoglobulin Heavy Chain ◽  
Chain Locus ◽  
Heavy Chain Locus

scholarly journals Genetic analysis of self-associating immunoglobulin G rheumatoid factors from two rheumatoid synovia implicates an antigen-driven response.

1992 ◽  
Vol 175 (3) ◽  
pp. 831-842 ◽  
Author(s):  
T Olee ◽  
E W Lu ◽  
D F Huang ◽  
R W Soto-Gil ◽  
M Deftos ◽  
...  
Keyword(s):  
Amino Acid ◽  
Heavy Chain ◽  
Immunoglobulin M ◽  
Natural Antibody ◽  
Antibody Repertoire ◽  
Rheumatoid Factors ◽  
Variable Regions ◽  
Genetic Origins ◽  
V Genes ◽  
Vh Gene

Although much has been learned about the molecular basis of immunoglobulin M (IgM) rheumatoid factors (RFs) in healthy individuals and in patients with mixed cryoglobulinemia and rheumatoid arthritis, little is known about the genetic origins of the potentially pathogenic IgG RFs in the inflamed rheumatoid synovia of patients. Recently, we generated from unmanipulated synovium B cells several hybridomas that secreted self-associating IgG RFs. To delineate the genetic origins of such potentially pathogenic RFs, we adapted the anchored polymerase chain reaction to rapidly clone and characterize the expressed Ig V genes for the L1 and the D1 IgG RFs. Then, we identified the germline counterparts of the expressed L1 IgG RF V genes. The results showed that the L1 heavy chain was encoded by a Vh gene that is expressed preferentially during early ontogenic development, and that is probably located within 240 kb upstream of the Jh locus. The overlap between this RF Vh gene and the restricted fetal antibody repertoire is reminiscent of the natural antibody-associated Vh genes, and suggests that at least part of the "potential pathogenic" IgG RFs in rheumatoid synovium may derive from the "physiological" natural antibody repertoire in a normal immune system. Indeed, the corresponding germline Vh gene for L1 encodes the heavy chain of an IgM RF found in a 19-wk-old fetal spleen. Furthermore, the comparisons of the expressed RF V genes and their germline counterparts reveal that the L1 heavy and light chain variable regions had, respectively, 16 and 7 somatic mutations, which resulted in eight and four amino acid changes. Strikingly, all eight mutations in the complementarity determining regions of the V gene-encoded regions were replacement changes, while only 6 of 11 mutations in the framework regions caused amino acid changes. Combined with L1's high binding affinity toward the Fc fragment, these results suggest strongly that the L1 IgG RF must have been driven by the Fc antigen.

Overexpression of HOXB7 and homeobox genes characterizes multiple myeloma patients lacking the major primary immunoglobulin heavy chain locus translocations

2011 ◽  
Vol 86 (12) ◽  
pp. E64-E66 ◽  
Author(s):  
Luca Agnelli ◽  
Paola Storti ◽  
Katia Todoerti ◽  
Gabriella Sammarelli ◽  
Benedetta Dalla Palma ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Heavy Chain ◽  
Homeobox Genes ◽  
Immunoglobulin Heavy Chain ◽  
Chain Locus ◽  
Heavy Chain Locus

Organization of the Human Immunoglobulin Heavy-Chain Locus

1993 ◽  
pp. 91-97
Author(s):  
Fumihiko Matsuda ◽  
Euy Kyun Shin ◽  
Hitoshi Nagaoka ◽  
Ryusuke Matsumura ◽  
Makoto Haino ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Immunoglobulin Heavy Chain ◽  
Human Immunoglobulin ◽  
Chain Locus ◽  
Heavy Chain Locus

scholarly journals Allelic Frequencies of 3' Ig Heavy Chain Locus Enhancer HS1,2-A Associated with Ig Levels in Patients with Schizophrenia

2009 ◽  
Vol 22 (1) ◽  
pp. 115-123 ◽  
Author(s):  
D. Frezza ◽  
V. Giambra ◽  
C. Mattioli ◽  
K. Piccoli ◽  
R. Massoud ◽  
...  
Keyword(s):  
Heavy Chain ◽  
Allelic Frequencies ◽  
Chain Locus ◽  
Heavy Chain Locus ◽  
Ig Heavy Chain

A second B cell-specific enhancer 3' of the immunoglobulin heavy-chain locus

Nature ◽  
1990 ◽  
Vol 344 (6262) ◽  
pp. 165-168 ◽  
Author(s):  
Sven Pettersson ◽  
Graham P. Cook ◽  
Marianne Brüggemann ◽  
Gareth T. Williams ◽  
Michael S. Neuberger
Keyword(s):  
B Cell ◽  
Heavy Chain ◽  
Immunoglobulin Heavy Chain ◽  
Chain Locus ◽  
Heavy Chain Locus

scholarly journals Molecular mechanisms involved in receptor editing at the Ig heavy chain locus.

1998 ◽  
Vol 10 (2) ◽  
pp. 241-246 ◽  
Author(s):  
L. Fanning ◽  
F. E. Bertrand ◽  
C. Steinberg ◽  
G. E. Wu
Keyword(s):  
Heavy Chain ◽  
Molecular Mechanisms ◽  
Receptor Editing ◽  
Chain Locus ◽  
Heavy Chain Locus ◽  
Ig Heavy Chain
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