Expression of ɛ germ-line gene transcripts and mRNA for the ɛ heavy chain of IgE in nasal B cells and the effects of topical corticosteroid

1997 ◽  
Vol 27 (11) ◽  
pp. 2899-2906 ◽  
Author(s):  
Stephen R. Durham ◽  
Hannah J. Gould ◽  
Cortlandt P. Thienes ◽  
Mikila R. Jacobson ◽  
Keisuke Masuyama ◽  
...  
Keyword(s):  
B Cells ◽  
Topical Corticosteroid ◽  
Heavy Chain ◽  
Germ Line ◽  
Gene Transcripts

scholarly journals Immunoglobulin gene rearrangements in normal mouse B cells

1982 ◽  
Vol 2 (7) ◽  
pp. 829-836
Author(s):  
P Early ◽  
C Nottenburg ◽  
I Weissman ◽  
L Hood
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Germ Line ◽  
Gene Segment ◽  
Immunoglobulin M ◽  
Chain Gene ◽  
Allelic Exclusion ◽  
Immunoglobulin Gene ◽  
Spleen Cells ◽  
Surface Immunoglobulin

We have analyzed the structure of rearranged mu heavy-chain genes obtained from the genomic DNA of normal BALB/c mouse spleen cells expressing surface immunoglobulin M. Examples were found of two types of nonproductive rearrangements, which may be responsible for allelic exclusion in normal B cells. In one of these rearrangements, a germ line D gene segment has joined to the JH4 gene segment but no V/D joining has occurred. We present evidence that D gene segments lie as a cluster between V and J gene segments in the germ line. A comparison of conserved sequences in V and D gene segments suggests that the D gene segments, which are found only in the heavy-chain gene family, may have evolved from V gene segments similar to the Vk family.

scholarly journals Immunoglobulin gene rearrangements in normal mouse B cells.

1982 ◽  
Vol 2 (7) ◽  
pp. 829-836 ◽  
Author(s):  
P Early ◽  
C Nottenburg ◽  
I Weissman ◽  
L Hood
Keyword(s):  
B Cells ◽  
Heavy Chain ◽  
Germ Line ◽  
Gene Segment ◽  
Immunoglobulin M ◽  
Chain Gene ◽  
Allelic Exclusion ◽  
Immunoglobulin Gene ◽  
Spleen Cells ◽  
Surface Immunoglobulin

We have analyzed the structure of rearranged mu heavy-chain genes obtained from the genomic DNA of normal BALB/c mouse spleen cells expressing surface immunoglobulin M. Examples were found of two types of nonproductive rearrangements, which may be responsible for allelic exclusion in normal B cells. In one of these rearrangements, a germ line D gene segment has joined to the JH4 gene segment but no V/D joining has occurred. We present evidence that D gene segments lie as a cluster between V and J gene segments in the germ line. A comparison of conserved sequences in V and D gene segments suggests that the D gene segments, which are found only in the heavy-chain gene family, may have evolved from V gene segments similar to the Vk family.

scholarly journals Identification of a germ line transcript from the unrearranged kappa gene in human B cells.

1989 ◽  
Vol 9 (10) ◽  
pp. 4560-4562 ◽  
Author(s):  
D J Martin ◽  
B G Van Ness
Keyword(s):  
B Cells ◽  
Cell Lines ◽  
Germ Line ◽  
Stages Of Development ◽  
Mrna Species ◽  
Human B Cells

A novel kappa immunoglobulin-hybridizing mRNA in cell lines derived from human B cells arrested at several stages of development has been identified. Hybridization studies demonstrate that this 1.5-kilobase mRNA species is the spliced product of a precursor germ line transcript initiating upstream of the unrearranged JKappa locus.

scholarly journals Molecular characteristics of antibodies bearing an anti-DNA-associated idiotype.

1991 ◽  
Vol 174 (6) ◽  
pp. 1639-1652 ◽  
Author(s):  
A Manheimer-Lory ◽  
J B Katz ◽  
M Pillinger ◽  
C Ghossein ◽  
A Smith ◽  
...  
Keyword(s):  
B Cells ◽  
Dna Binding ◽  
Lupus Erythematosus ◽  
Germ Line ◽  
High Titer ◽  
Variable Region ◽  
Amino Acid Sequences ◽  
Molecular Characteristics ◽  
Systemic Lupus ◽  
Dna Antibodies

Anti-double-stranded DNA antibodies are the hallmark of the disease systemic lupus erythematosus and are believed to contribute to pathogenesis. While a large number of anti-DNA antibodies from mice with lupus-like syndromes have been characterized and their variable region genes sequenced, few human anti-DNA antibodies have been reported. We describe here the variable region gene sequences of eight antibodies produced by Epstein-Barr virus (EBV)-transformed B cells that bear the 3I idiotype, an idiotype expressed on anti-DNA antibodies and present in high titer in patients with systemic lupus. The comparison of these antibodies to the light chains of 3I+ myeloma proteins and serum antibodies reveals that EBV transformation yields B cells producing antibodies representative of the expressed antibody repertoire. The analysis of nucleotide and amino acid sequences of these antibodies suggests the first complementarity determining region of the light chain may be important in DNA binding and that paradigms previously generated to account for DNA binding require modification. The understanding of the molecular genetics of the anti-DNA response requires a more complete description of the immunoglobulin germ line repertoire, but data reported here suggest that somatic diversification is a characteristic of the anti-DNA response.

scholarly journals Critical roles of the immunoglobulin intronic enhancers in maintaining the sequential rearrangement of IgH and Igk loci

2006 ◽  
Vol 203 (7) ◽  
pp. 1721-1732 ◽  
Author(s):  
Matthew A. Inlay ◽  
Tongxiang Lin ◽  
Heather H. Gao ◽  
Yang Xu
Keyword(s):  
B Cells ◽  
Developmental Stage ◽  
Heavy Chain ◽  
Light Chain ◽  
Matrix Attachment Region ◽  
Cis Elements ◽  
Wild Type ◽  
Intronic Enhancer ◽  
Attachment Region

V(D)J recombination of immunoglobulin (Ig) heavy (IgH) and light chain genes occurs sequentially in the pro– and pre–B cells. To identify cis-elements that dictate this order of rearrangement, we replaced the endogenous matrix attachment region/Igk intronic enhancer (MiEκ) with its heavy chain counterpart (Eμ) in mice. This replacement, denoted EμR, substantially increases the accessibility of both Vκ and Jκ loci to V(D)J recombinase in pro–B cells and induces Igk rearrangement in these cells. However, EμR does not support Igk rearrangement in pre–B cells. Similar to that in MiEκ−/− pre–B cells, the accessibility of Vκ segments to V(D)J recombinase is considerably reduced in EμR pre–B cells when compared with wild-type pre–B cells. Therefore, Eμ and MiEκ play developmental stage-specific roles in maintaining the sequential rearrangement of IgH and Igk loci by promoting the accessibility of V, D, and J loci to the V(D)J recombinase.

Stereotyped patterns of somatic hypermutation in subsets of patients with chronic lymphocytic leukemia: implications for the role of antigen selection in leukemogenesis

Blood ◽  
2008 ◽  
Vol 111 (3) ◽  
pp. 1524-1533 ◽  
Author(s):  
Fiona Murray ◽  
Nikos Darzentas ◽  
Anastasia Hadzidimitriou ◽  
Gerard Tobin ◽  
Myriam Boudjogra ◽  
...  
Keyword(s):  
Amino Acid ◽  
Chronic Lymphocytic Leukemia ◽  
Heavy Chain ◽  
Germ Line ◽  
Somatic Hypermutation ◽  
Lymphocytic Leukemia ◽  
Chain Gene ◽  
Distinctive Features ◽  
Ighv Gene ◽  
Gene Usage

Abstract Somatic hypermutation (SHM) features in a series of 1967 immunoglobulin heavy chain gene (IGH) rearrangements obtained from patients with chronic lymphocytic leukemia (CLL) were examined and compared with IGH sequences from non-CLL B cells available in public databases. SHM analysis was performed for all 1290 CLL sequences in this cohort with less than 100% identity to germ line. At the cohort level, SHM patterns were typical of a canonical SHM process. However, important differences emerged from the analysis of certain subgroups of CLL sequences defined by: (1) IGHV gene usage, (2) presence of stereotyped heavy chain complementarity-determining region 3 (HCDR3) sequences, and (3) mutational load. Recurrent, “stereotyped” amino acid changes occurred across the entire IGHV region in CLL subsets carrying stereotyped HCDR3 sequences, especially those expressing the IGHV3-21 and IGHV4-34 genes. These mutations are underrepresented among non-CLL sequences and thus can be considered as CLL-biased. Furthermore, it was shown that even a low level of mutations may be functionally relevant, given that stereotyped amino acid changes can be found in subsets of minimally mutated cases. The precise targeting and distinctive features of somatic hypermutation (SHM) in selected subgroups of CLL patients provide further evidence for selection by specific antigenic element(s).

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