scholarly journals Sequence of a cDNA encoding Basilea kappa light chains (K2 isotype) suggests a possible relationship of protein structure to limited expression.

1984 ◽  
Vol 159 (2) ◽  
pp. 635-640 ◽  
Author(s):  
K E Bernstein ◽  
E Lamoyi ◽  
N McCartney-Francis ◽  
R G Mage
Keyword(s):  
Sulfhydryl Group ◽  
Variable Region ◽  
Complete Sequence ◽  
Light Chains ◽  
Small Subset ◽  
Constant Region ◽  
Region Gene ◽  
Variable Regions ◽  
Immunoglobulin Kappa ◽  
Kappa Light Chains

We present the complete sequence of a cDNA encoding rabbit immunoglobulin kappa light chains of the Basilea isotype (K2). Although all rabbits seem to possess a K2 constant region gene, expression of this gene in most rabbits is minimal if present at all. Even in Basilea rabbits the majority of expressed immunoglobulins are of lambda type. We find that the sequence of our Basilea cDNA constant region and the sequence of a "silent" K2 gene from b4 rabbits (bas-N4) are almost identical. The bas (K2) isotype lacks cysteine at position 171 in the constant region that is present in all K1 constant regions and usually forms an interdomain disulfide bond, with a cysteine at position 80 of the variable region. We postulate that one factor contributing to the low expression of the bas (K2) isotype could be a paucity of V kappa regions lacking cysteine at position 80. If a typical rabbit V kappa encoding Cys at position 80 is rearranged and expressed with th K2 isotype. B cells with mRNAs encoding light chains with free sulfhydryl groups would result. These cells may fail to form functional immunoglobulin receptors. Only a small subset of rabbit variable regions that lack the cysteine at position 80 would rearrange and encode K2 light chains lacking a free sulfhydryl group.

scholarly journals Sequence of the full-length immunoglobulin κ-chain of mouse myeloma MPC 11

1978 ◽  
Vol 171 (2) ◽  
pp. 337-347 ◽  
Author(s):  
G P Smith
Keyword(s):  
Variable Region ◽  
Full Length ◽  
Light Chains ◽  
Its Sequence ◽  
Heavy Chains ◽  
Immunoglobulin Kappa ◽  
N Terminus ◽  
Kappa Chain ◽  
Kappa Light Chains ◽  
Mouse Myeloma

MPC 11 mouse myeloma cells synthesize two immunoglobulin kappa light chains, coded by two separate genes. One of these Kappa-chains has no variable region and is degraded intracellularly. The other is a full-length kappa-chain contaning both variable and constant regions: this chain is secreted, both by itself and combined with heavy chains in molecules of immunoglobulin G. This paper reports the amino acid sequence of the myeloma MPC 11 full-length kappa-chain. The chain is unusual in having 12 extra residues at its N-terminus when its sequence is aligned with those of other mouse kappa-chains; no other anomalies were found in its sequence.

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 The Activation-induced Deaminase Functions in a Postcleavage Step of the Somatic Hypermutation Process

2002 ◽  
Vol 195 (9) ◽  
pp. 1193-1198 ◽  
Author(s):  
F. Nina Papavasiliou ◽  
David G. Schatz
Keyword(s):  
Somatic Hypermutation ◽  
Cytidine Deaminase ◽  
Point Mutations ◽  
Dna Lesions ◽  
Dominant Negative ◽  
Constant Region ◽  
Region Gene ◽  
Variable Regions ◽  
Class Switch ◽  
Activation Induced Deaminase

Activation of B cells by antigen fuels two distinct molecular modifications of immunoglobulin (Ig) genes. Class-switch recombination (CSR) replaces the Igμ heavy chain constant region with a downstream constant region gene, thereby altering the effector function of the resulting antibodies. Somatic hypermutation (SHM) introduces point mutations into the variable regions of Ig genes, thereby changing the affinity of antibody for antigen. Mechanistic overlap between the two reactions has been suggested by the finding that both require the activation-induced cytidine deaminase (AID). It has been proposed that AID initiates both CSR and SHM by activating a common nuclease. Here we provide evidence that cells lacking AID, or expressing a dominant negative form of the protein, are still able to incur DNA lesions in SHM target sequences. The results indicate that an intact cytidine deaminase motif is required for AID function, and that AID acts downstream of the initial DNA lesions in SHM.

scholarly journals Expression of a public idiotype by human monoclonal IgM directed to myelin-associated glycoprotein and characterization of the variability subgroup of their heavy and light chains.

1989 ◽  
Vol 170 (5) ◽  
pp. 1551-1558 ◽  
Author(s):  
J C Brouet ◽  
K Dellagi ◽  
M C Gendron ◽  
A Chevalier ◽  
C Schmitt ◽  
...  
Keyword(s):  
Nonhuman Primate ◽  
Light Chains ◽  
Antibody Activity ◽  
Rheumatoid Factors ◽  
Variable Regions ◽  
Cold Agglutinins ◽  
Heavy Chains ◽  
Myelin Associated Glycoprotein ◽  
Kappa Light Chains

Most studies using rabbit or mouse antisera failed to detect CRI between human IgM directed to MAG. We show here that 9 of 10 such IgM express a public CRI as defined by a nonhuman primate antiserum. Shared idiotype is likely involved in (or close to) the combining site of those IgM since antiidiotypic serum inhibited the binding of IgM to MAG and reacted with IgM having different variable regions of light and heavy chains. Partial aminoterminal sequence of heavy and light chains showed that anti-MAG IgM use either lambda chains (one IgM) or kappa light chains (six IgM) of different variability subgroups (V kappa IV in three instances, V kappa I in two, and V kappa II in one), whereas heavy chains belong to the VHIII (six IgM) or to the VHII (1 IgM) subgroup. These features distinguish these IgM from other human monoclonal IgM with a defined antibody activity, such as rheumatoid factors or cold agglutinins.

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.

Allotypic marker of kappa light chains of rat immunoglobulins localized in the constant region of the chain

1974 ◽  
Vol 11 (8) ◽  
pp. 517-518 ◽  
Author(s):  
R.S Nezlin ◽  
T.I Vengerova ◽  
O.V Rokhlin ◽  
H.K.G Machulla
Keyword(s):  
Light Chains ◽  
Constant Region ◽  
Kappa Light Chains ◽  
Allotypic Marker

scholarly journals AN ANALYSIS OF THE SEQUENCES OF THE VARIABLE REGIONS OF BENCE JONES PROTEINS AND MYELOMA LIGHT CHAINS AND THEIR IMPLICATIONS FOR ANTIBODY COMPLEMENTARITY

1970 ◽  
Vol 132 (2) ◽  
pp. 211-250 ◽  
Author(s):  
Tai Te Wu ◽  
Elvin A. Kabat
Keyword(s):  
Sequence Data ◽  
Variable Region ◽  
High Variability ◽  
Light Chains ◽  
Variable Regions ◽  
Advantages And Disadvantages ◽  
Specific Subgroup ◽  
Species Specific ◽  
Specific Species ◽  
Bence Jones Proteins

In an attempt to account for antibody specificity and complementarity in terms of structure, human κ-, human λ-, and mouse κ-Bence Jones proteins and light chains are considered as a single population and the variable and constant regions are compared using the sequence data available. Statistical criteria are used in evaluating each position in the sequence as to whether it is essentially invariant or group-specific, subgroup-specific, species-specific, etc. Examination of the invariant residues of the variable and constant regions confirms the existence of a large number of invariant glycines, no invariant valine, lysine, and histidine, and only one invariant leucine and alanine in the variable region, as compared with the absence of invariant glycines and presence of three each of invariant alanine, leucine, and valine and two each of invariant lysine and histidine in the constant region. The unique role of glycine in the variable region is emphasized. Hydrophobicity of the invariant residues of the two regions is also evaluated. A parameter termed variability is defined and plotted against the position for the 107 residues of the variable region. Three stretches of unusually high variability are noted at residues 24–34, 50–56, and 89–97; variations in length have been found in the first and third of these. It is hypothesized that positions 24–34 and 89–97 contain the complementarity-determining residues of the light chain—those which make contact with the antigenic determinant. The heavy chain also has been reported to have a similar region of very high variability which would also participate in forming the antibody-combining site. It is postulated that the information for site complementarity is contained in some extrachromosomal DNA such as an episome and is incorporated by insertion into the DNA of the structural genes for the variable region of short linear sequences of nucleotides. The advantages and disadvantages of this hypothesis are discussed.

scholarly journals Autoantibody-associated cross-reactive idiotypes expressed at high frequency in chronic lymphocytic leukemia relative to B-cell lymphomas of follicular center cell origin

Blood ◽  
1988 ◽  
Vol 72 (2) ◽  
pp. 422-428 ◽  
Author(s):  
TJ Kipps ◽  
BA Robbins ◽  
P Kuster ◽  
DA Carson
Keyword(s):  
Chronic Lymphocytic Leukemia ◽  
B Cell ◽  
Light Chain ◽  
Variable Region ◽  
Lymphocytic Leukemia ◽  
Kappa Light Chain ◽  
Region Gene ◽  
Variable Regions ◽  
Hodgkin's Lymphomas ◽  
Center Cell

Using murine monoclonal antibodies (MoAbs) specific for immunoglobulin (Ig) cross-reactive idiotypes (CRI), we performed immunohistochemical analyses on frozen tissue sections and cytocentrifuge preparations of Ig-expressing malignant cells from patients with chronic lymphocytic leukemia (CLL) and B-cell non-Hodgkin's lymphomas (NHL) of follicular center cell origin. Twenty percent (4/20) of the Ig kappa light chain- expressing CLL cells reacted with 17.109, a MoAb against a major CRI on human IgM autoantibodies that is encoded by a conserved Ig variable- region gene (V gene) of the V kappa IIIb sub-subgroup. Another MoAb specific for V kappa IIIb framework determinant(s) reacted exclusively with all the 17.109-reactive CLL cells. Only one of 20 kappa light- chain-expressing CLL cells reacted with 6B6.6, a monoclonal antibody specific for a CRI commonly found on rheumatoid factor (RF) paraproteins with light-chain variable regions of the V kappa IIIa sub- subgroup. Finally, greater than 20% (8/34) of all CLL reacted with G6, a MoAb specific for an Ig heavy chain-associated CRI present on several RF paraproteins. In contrast, these CRIs were expressed at significantly lower frequencies in NHL of follicular center cell origin. Only one of 30 NHL expressing kappa light chains reacted with the 17.109 MoAb. Also, in contrast to the concordance between the 17.109-CRI and V kappa IIIb framework determinant(s) in CLL, two lymphomas in addition to the 17.109-reactive lymphoma were recognized by the anti-V kappa IIIb framework MoAb. None of the NHL reacted with either the 6B6.6 or the G6 MoAbs. These results are the first to demonstrate that CLL and NHL differ with respect to the expression of autoantibody-associated CRIs. The data support the notion that NHL of follicular center cell origin differs from CLL in its utilization and/or somatic mutation of Ig variable-region genes. The physiological and immunotherapeutic implications of these findings are discussed.

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