scholarly journals Variable region sequences of murine IgM anti-IgG monoclonal autoantibodies (rheumatoid factors). A structural explanation for the high frequency of IgM anti-IgG B cells.

1986 ◽  
Vol 164 (2) ◽  
pp. 407-427 ◽  
Author(s):  
M J Shlomchik ◽  
D A Nemazee ◽  
V L Sato ◽  
J Van Snick ◽  
D A Carson ◽  
...  
Keyword(s):  
B Cells ◽  
Variable Region ◽  
Amino Acid Sequences ◽  
Light Chains ◽  
Binding Interaction ◽  
Structural Explanation ◽  
Region Gene ◽  
Unique Type ◽  
Heavy Chains ◽  
Germline Genes

The nucleotide sequences of heavy and light chains from 10 monoclonal IgM anti-IgG1 (RF) antibodies were determined and reported here as translated amino acid sequences. Only three families of VK light chains were used in these antibodies: VK1 (two examples), VK8 (three examples), and VK19 (four examples). This represents a significant nonrandom selection of light chains. In contrast, all other variable region gene segments (i.e., VH, DH, JH, and JK) were used in a pattern consistent with random selection from the available pool of germline genes. In two cases, the same anti-IgG1 specificity was generated by a combination of very homologous light chains with unrelated heavy chains. We infer from this that the light chain is the segment used by these antibodies to bind IgG1. The nature of these sequences provides an explanation for the curious observation that as many as 15% of splenic B cells in normal mice may be expressing IgM anti-IgG; if, as our data suggest, certain light chains in combination with many different heavy chains can be used in assembling the anti-IgG specificity, then, because of combinatorial association in which the heavy chain is not relevant for specificity, the fraction of IgM-producing B cells expressing these light chains should approximate the fraction of B cells making IgM anti-IgG. We calculate, based on data presented in several other studies, that 5-17% of B cells express one of the VK types observed in monoclonal RF. This agrees well with estimates for the number of B cells making IgM anti-IgG. In addition, our findings could rule out other explanations of the high percentage of B cells making RF, such as constant stimulation by antigen or presence of numerous antigenic epitopes since it was shown that IgM anti-IgG1 antibodies are not somatically mutated and that they are structurally homogeneous. We aligned the VK sequences of the RF in hopes of finding some primary sequence homology between the represented VK families which might point to residues involved in the binding interaction. Although we found no such homology in the hypervariable regions, we did find significant and unexpected homology in the FR2 and FR3 of these light chains. We noted that these regions are exposed in the Ig structure and postulate that they may be involved in a unique type of binding interaction between two Ig family domains, i.e., VK binding to a constant region domain of IgG.

scholarly journals The amino acid sequences of the Fd fragments of two human γ 1 heavy chains

1970 ◽  
Vol 117 (4) ◽  
pp. 641-660 ◽  
Author(s):  
E. M. Press ◽  
N. M. Hogg
Keyword(s):  
Amino Acid ◽  
Aspartic Acid ◽  
Heavy Chain ◽  
Variable Region ◽  
Amino Acid Sequences ◽  
Light Chains ◽  
Aspartic Acid Residue ◽  
Variable Regions ◽  
Heavy Chain Variable Region ◽  
Heavy Chains

The amino acid sequences of the Fd fragments of two human pathological immunoglobulins of the immunoglobulin G1 class are reported. Comparison of the two sequences shows that the heavy-chain variable regions are similar in length to those of the light chains. The existence of heavy chain variable region subgroups is also deduced, from a comparison of these two sequences with those of another γ 1 chain, Eu, a μ chain, Ou, and the partial sequence of a fourth γ 1 chain, Ste. Carbohydrate has been found to be linked to an aspartic acid residue in the variable region of one of the γ 1 chains, Cor.

scholarly journals Differential usage of an Ig heavy chain variable region gene by human B- cell tumors

Blood ◽  
1993 ◽  
Vol 82 (1) ◽  
pp. 224-230 ◽  
Author(s):  
FK Stevenson ◽  
MB Spellerberg ◽  
J Treasure ◽  
CJ Chapman ◽  
LE Silberstein ◽  
...  
Keyword(s):  
Amino Acid ◽  
B Cells ◽  
B Cell ◽  
Gene Segment ◽  
Variable Region ◽  
Amino Acid Substitutions ◽  
Region Gene ◽  
Heavy Chains ◽  
Vh Gene ◽  
Histologic Types

A monoclonal anti-idiotypic antibody has been raised that recognizes Igs with heavy chains encoded by a member of the VH4 family, the VH4–21 gene segment. The idiotope (Id) is detectable on a high percentage of early B cells in fetal spleen, and is expressed by certain autoantibodies, particularly cold-reactive anti-red blood cell antibodies. Therefore, it was of interest to investigate usage of this VH gene by neoplastic B cells; 81 chronic lymphocytic leukemias (CLLs) involving CD5+ B cells and 62 B-cell lymphomas of varying histologic type have been analyzed. The Id was expressed by only 3 of 81 (3.7%) of the CLLs, indicating a relatively low usage by these tumors. In contrast, the Id was expressed by 9 of 62 (14.5%) of the lymphomas across a range of histologic types, indicating a differential use of the VH4–21 gene among B-cell neoplasms. For three of the Id-positive lymphomas, each of a different histologic class, the nucleotide sequence of the tumor-derived VH gene was determined; the VH4–21 gene was identified, as expected. The sequence from the CLL was identical to the germline sequence, and the marginal zone lymphoma showed only 3 nucleotide changes, 2 of which gave rise to amino acid substitutions. In contrast, the sequence from the follicular lymphoma showed 29 nucleotide changes giving rise to 14 amino acid substitutions, which were scattered among the CDR and FW regions.

scholarly journals Complete amino acid sequences of variable regions of two human IgM rheumatoid factors, BOR and KAS of the Wa idiotypic family, reveal restricted use of heavy and light chain variable and joining region gene segments.

1987 ◽  
Vol 166 (2) ◽  
pp. 550-564 ◽  
Author(s):  
M M Newkirk ◽  
R A Mageed ◽  
R Jefferis ◽  
P P Chen ◽  
J D Capra
Keyword(s):  
Amino Acid ◽  
Gene Segment ◽  
Variable Region ◽  
Amino Acid Sequences ◽  
Light Chains ◽  
Rheumatoid Factors ◽  
Region Gene ◽  
Variable Regions ◽  
D Region ◽  
Restricted Use

Evidence derived from the complete amino acid sequences of the variable regions of both the heavy and light chains of two members (BOR and KAS) of the Wa idiotypic family of human rheumatoid factors suggests that not only are the light chains of these molecules derived from possibly one variable region gene segment, but the heavy chain variable regions are all derived from the VHI subgroup of human V region genes. These molecules exhibit a surprising conservation in the size of D region, and all use the JH4 gene element. This restriction in use of VL, VH, D, and JH suggests all of these elements may play a crucial role in either antigen binding and/or expression of the crossreactive idiotype.

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 Fate of surrogate light chains in B lineage cells.

1996 ◽  
Vol 183 (2) ◽  
pp. 421-429 ◽  
Author(s):  
K Lassoued ◽  
H Illges ◽  
K Benlagha ◽  
M D Cooper
Keyword(s):  
B Cells ◽  
Cell Surface ◽  
Light Chain ◽  
Light Chains ◽  
Receptor Complex ◽  
Surrogate Light Chain ◽  
Heavy Chains ◽  
Receptor Component ◽  
B Lineage ◽  
Receptor Assembly

Biosynthesis of the immunoglobulin (Ig) receptor components and their assembly were examined in cell lines representative of early stages in human B lineage development. In pro-B cells, the nascent surrogate light chain proteins form a complex that transiently associates in the endoplasmic reticulum with a spectrum of unidentified proteins (40, 60, and 98 kD) and Bip, a heat shock protein family member. Lacking companion heavy chains, the surrogate light chains in pro-B cells do not associate with either the Ig(alpha) or Ig(beta) signal transduction units, undergo rapid degradation, and fail to reach the pro-B cell surface. In pre-B cells, by contrast, a significant portion of the surrogate light chain proteins associate with mu heavy chains, Ig(alpha), and Ig(beta) to form a stable receptor complex with a relatively long half-life. Early in this assembly process, Bip/GRP78, calnexin, GRP94, and a protein of approximately 17 kD differentially bind to the nascent mu heavy chains. The 17-kD intermediate is gradually replaced by the surrogate light chain protein complex, and the Ig(alpha) and Ig(beta) chains bind progressively to the mu heavy chains during the complex and relatively inefficient process of pre-B receptor assembly. The results suggest that, in humans, heavy chain association is essential for surrogate light chain survival and transport to the cell surface as an integral receptor component.

Introduced T cell receptor variable region gene segments recombine in pre-B cells: Evidence that B and T cells use a common recombinase

Cell ◽  
1986 ◽  
Vol 44 (2) ◽  
pp. 251-259 ◽  
Author(s):  
George D. Yancopoulos ◽  
T.Keith Blackwell ◽  
Heikyung Suh ◽  
Leroy Hood ◽  
Frederick W. Alt
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Receptor ◽  
Variable Region ◽  
Cell Receptor ◽  
Region Gene ◽  
Variable Region Gene

Evidence that murine pre-B cells synthesise μ heavy chains but no light chains

Nature ◽  
1979 ◽  
Vol 280 (5725) ◽  
pp. 838-841 ◽  
Author(s):  
PETER BURROWS ◽  
MARK LEJEUNE ◽  
JOHN F. KEARNEY
Keyword(s):  
B Cells ◽  
Light Chains ◽  
Heavy Chains

scholarly journals T and B cells that recognize the same antigen do not transcribe similar heavy chain variable region gene segments.

1983 ◽  
Vol 158 (1) ◽  
pp. 192-209 ◽  
Author(s):  
E Kraig ◽  
M Kronenberg ◽  
J A Kapp ◽  
C W Pierce ◽  
A F Abruzzini ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
Cell Lines ◽  
Variable Region ◽  
Antigenic Specificity ◽  
Helper T Cell ◽  
Region Gene ◽  
Vh Gene ◽  
T Cell Lines

We have attempted to determine whether T cells and B cells that have the same antigenic specificity and whose receptors share idiotypic determinants in fact express similar VH gene segments. To do this, we have obtained and characterized a cDNA clone containing the entire coding sequence for the VH gene from a glutamic acid60/alanine30/tyrosine10 (GAT)-binding immunoglobulin that carries the CGAT idiotype. The GAT-VH clone was hybridized to Northern blots of GAT-specific T cell RNAs; there was no evidence of a T cell transcript that hybridized to the GAT-VH probe. The T cells analyzed included: (a) 10 GAT-binding suppressor T cell hybridomas, 6 of which secreted factors with CGAT idiotypic determinants, (b) one GAT-specific helper T cell hybridoma, and (c) two GAT-specific helper T cell lines grown in the absence of feeder cells. The detection limit of the Northern blot analysis was 1-2 copies of a particular mRNA species per cell for the hybridomas and 5-10 copies per cell for the T cell lines. Therefore, we conclude that T and B lymphocytes responding to GAT do not utilize similar VH gene segments. Furthermore, the presence of idiotypic determinants on T lymphocytes does not necessarily imply close structural similarity between T and B cell antigen receptors.

scholarly journals Restricted immunoglobulin variable region gene usage by normal Ly-1 (CD5+) B cells that recognize phosphatidyl choline.

1989 ◽  
Vol 169 (6) ◽  
pp. 1869-1877 ◽  
Author(s):  
T J Mercolino ◽  
A L Locke ◽  
A Afshari ◽  
D Sasser ◽  
W W Travis ◽  
...  
Keyword(s):  
B Cells ◽  
Phosphatidyl Choline ◽  
Mammalian Cells ◽  
Variable Region ◽  
Normal Adult ◽  
Region Gene ◽  
Fragment Analysis ◽  
Gene Usage ◽  
Variable Region Genes ◽  
Immunoglobulin Variable Region Gene

5-15% of lymphocytes in the peritoneums of normal adult B10.H-2aH-4bp/Wts (2a4b) mice are CD5+ (Ly-1) B cells that recognize phosphatidyl choline (PtC), a phospholipid component of all mammalian cells. We produced a set of IgM-secreting hybridomas from the peritoneal cells of normal, adult 2a4b mice. We found that this set of hybridomas shows a similarly high frequency of antibodies specific for PtC (21 of 86) that also react with bromelain-treated mouse erythrocytes. Restriction fragment analysis of Ig gene rearrangements and analysis of expressed Ig idiotypes reveal that these cells use a restricted set of variable region genes to generate the PtC-specific antibodies. The Ig genes used by the PtC-specific hybridomas appear to be the same as those found in the PtC-specific Ly-1 B cell lymphomas, CH27 and CH34.

Biased immunoglobulin variable region gene expression by Ly-1 B cells due to clonal selection

1989 ◽  
Vol 19 (7) ◽  
pp. 1289-1295 ◽  
Author(s):  
Christopher A. Pennell ◽  
Thomas J. Mercolino ◽  
Therese A. Grdina ◽  
Larry W. Arnold ◽  
Geoffrey Haughton ◽  
...  
Keyword(s):  
Gene Expression ◽  
B Cells ◽  
Clonal Selection ◽  
Variable Region ◽  
Region Gene ◽  
Immunoglobulin Variable Region ◽  
Variable Region Gene ◽  
Immunoglobulin Variable Region Gene
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