scholarly journals A major group of mouse kappa chains controlled by the chromosome 6 locus, IgK-Ef2.

1980 ◽  
Vol 152 (3) ◽  
pp. 555-564 ◽  
Author(s):  
C Lazure ◽  
W T Hum ◽  
D M Gibson
Keyword(s):  
Light Chain ◽  
Normal Mouse ◽  
Variable Region ◽  
Normal Serum ◽  
Light Chains ◽  
Mouse Serum ◽  
Chromosome 6 ◽  
Frequency Of Occurrence ◽  
Myeloma Proteins ◽  
Normal Light

We previously demonstrated that loci closely linked to the Ly-3 locus control the expression of distinct sets of light chains in normal mouse serum immunoglobulin. One of these loci, IgK-Ef2, was shown to control two major bands in normal light chain isoelectric focusing (IF) profiles. Strains possessing the marker bands were designated IgK-Ef2a. Screening of myeloma proteins from the strains BALB/c (IgK-Ef2a) and NZB (IgK-Ef2b) led to the identification of eight proteins in the BALB/c collection having light chains that cofocus precisely with the polymorphic IF bands observed in normal serum light chains. Partial sequence analysis of 3 of the light chains has shown that they are all identical in the first 30 positions, which indicates that they constitute a single variable region of the kappa light chain (VK) group (VK1). The frequency of occurrence of the group within the BALB/c myeloma collections (8 out of 277) suggests that the number of such groups may be closer to 50 than to 100. The finding supports an interpretation of the genetic polymorphism as being in part a result of the absence of genes related to VK1 in IgK-Ef2b strains of mice.

scholarly journals The natural abundance of lambda2-light chains in inbred mice.

1978 ◽  
Vol 148 (5) ◽  
pp. 1388-1399 ◽  
Author(s):  
T Cotner ◽  
H N Eisen
Keyword(s):  
Amino Acid ◽  
Light Chain ◽  
Inbred Mice ◽  
Inbred Mouse ◽  
Variable Region ◽  
Fold Increase ◽  
Light Chains ◽  
Mouse Strains ◽  
Mouse Serum ◽  
Myeloma Protein

The amino acid sequence of the constant (C) domain of the light chain of the mouse myeloma protein M315 has not been identified so far in any other myeloma protein. In this study, serological analysis with antiserum to the C-domain of this light chain (L315) showed that approximately equal to 1% of Igs in normal mouse serum have L chains of the L315 type (called lambda2). Corroborative evidence was obtained by analysis of the carboxyterminal amino acid removed from normal light chains by carboxypeptidase A. A survey of 35 inbred mouse strains showed that all had lambda2; the serum level of Igs with lambda2-chains ranged from approximately equal to 140 microgram/ml in AL/N mice to approximately equal to 25 microgram/ml in SJL, BSVS, and eight other strains. In accord with the anti-Dnp activity of M315, sera from mice immunized with Dnp-KLH had three- to fivefold more lambda2 than sera from control mice immunized with KLH. It was also possible to measure serum immunoglobulin molecules bearing the lambda2 variable region of M315 (VL315). In BALB/c sera, the concentration of VL315 was about sixfold lower than that measured for lambda2. Thus, lambda2-chains are divided into at least two subsets: those whose V domain is indistinguishable from VL315 and those whose VL differs from VL315. A 10-fold increase in VL315 was obtained by immunizing BALB/c mice with Dnp-KLH. The relationship of the VL domains of normal immunoglobulin lambda2-chains to the embryonic Vlambda gene recently sequenced by Tonegawa et al., is discussed.

scholarly journals Ef2: a new LY-3-linked light-chain marker expressed in normal mouse serum immunoglobulin.

1979 ◽  
Vol 149 (6) ◽  
pp. 1477-1486 ◽  
Author(s):  
D M Gibson ◽  
S J MacLean
Keyword(s):  
Light Chain ◽  
Normal Mouse ◽  
Inbred Strains ◽  
Serum Immunoglobulin ◽  
Mouse Serum ◽  
Immunoglobulin Light Chains ◽  
Genetic Studies ◽  
Normal Mouse Serum ◽  
Normal Light ◽  
Gel Isoelectric Focusing

A new light-chain marker has been detected in normal mouse serum immunoglobulin light chains by gel isoelectric focusing. The marker (Ef2) involves the presence of two major and several minor bands in the normal light-chain IF profiles. Strains expressing the marker IF bands are designated Igk-Ef2a, whereas those lacking the bands are Igk-Ef2b. The majority of inbred strains are Igk-Ef2a. Strains found to be Igk-Ef2b are NZB/BlNJ, BDP/J, C58/J, I/LnJ, CE/J, and P/J. The strain distribution of the alleles differs from the distribution of alleles at the Ly-2 and Ly-3 loci, suggesting the new marker may represent a separate locus. Genetic studies have shown that Igk-Ef2 locus is closely linked to Igk-Ef1 and Hd loci on Chromosome 6, indicating that it is also closely linked to Ly-3. The relative importance of the bands controlled by the Igk-Ef2 locus suggests that the entire normal light-chain pool could be controlled by as few as 100 such loci.

scholarly journals The specificity of chain interactions among immunoglobulins. Combinations of γ chains with κ chains of the same subgroup as in the parent immunoglobulin G

1974 ◽  
Vol 139 (2) ◽  
pp. 369-374 ◽  
Author(s):  
G. T. Stevenson ◽  
L. E. Mole
Keyword(s):  
Immunoglobulin G ◽  
Structural Information ◽  
Variable Region ◽  
Light Chains ◽  
Predominant Role ◽  
Variable Regions ◽  
Human Immunoglobulins ◽  
Myeloma Proteins ◽  
Standard Population ◽  
Normal Light

1. The specificity of combination of heavy and light chains from selected human immunoglobulins was examined in the light of greater structural information than in previous studies. Heavy (γ) chains from immunoglobulin G (κ) myeloma proteins were allowed to combine with their homologous light (κ) chains or with other κ chains of the same variable-region subgroup. The affinity of each such pairing was assessed by having the test κ chain compete with a standard population of normal light chains. 2. There was a spread of affinities among the heavy–light pairings with the homologous pairings having an average affinity significantly higher than the heterologous pairings. 3. It follows that (a) the preference shown for homologous heavy–light pairings is not explicable simply in terms of the known subdivisions of the variable and constant regions of the chains, and (b) it is unlikely that those residues specifying the subgroups of κ-chain variable regions have a predominant role in the formation of interchain bonds with the γ-chain variable regions.

Antigenische Klassifizierung der Paraproteine und normalen Immunoglobuline vom Lambda-Typ / Paraproteins and Normal Immunoglobulins of the Lambda Type: Immunochemical Differentiation and Classification

1971 ◽  
Vol 26 (12) ◽  
pp. 1292-1302 ◽  
Author(s):  
F. W. Tischendorf
Keyword(s):  
Amino Acid ◽  
Amino Acid Sequence ◽  
Light Chain ◽  
Variable Region ◽  
Basic Amino Acid ◽  
Light Chains ◽  
Antigenic Sites ◽  
Normal Individuals ◽  
Normal Light ◽  
Bence Jones Proteins

The elaboration of antisera recognizing antigenic sites of the variable region of pathological immunoglobulin λ chains (Bence-Jones-proteins) is described. The antisera react with the (St+) marker carried by Bence-Jones-proteins of the basic amino-acid sequence VλI and the (111+) marker carried by L-chains of the basic sequence VλIII. With these antisera three specificityregion subtypes of human λ immunoglobulin chains could be distinguished antigenically. Twenty randomly chosen normal individuals were shown to be associated with λ chains of both basic sequences, VλI and VλIII. The results provide evidence for the non-allelic nature of the two aminoterminal light chain forms (p<0.001) and suggest that the basic sequences VλI and VλIII of Bence-Jones-proteins represent two distinct subgroups of normal light chains.

scholarly journals Monoclonal anti-light chain idiotype as a tumor-specific probe for human neoplastic B lymphocytes

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 919-923 ◽  
Author(s):  
M Wrightham ◽  
AL Tutt ◽  
MJ Glennie ◽  
TJ Hamblin ◽  
GT Stevenson ◽  
...  
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
B Lymphocytes ◽  
Light Chain ◽  
Normal Serum ◽  
Lymphocytic Leukemia ◽  
Light Chains ◽  
Specific Probe ◽  
Tonsillar Cells ◽  
Binding Curves

Abstract Tumor cells from patients with B cell neoplasms often secrete small amounts of free monoclonal light chains that can be found in the urine. Such tumor-derived light chains of the lambda type from a patient with typical chronic lymphocytic leukemia have been used to raise mouse monoclonal antibodies (MoAbs). A hybridoma-secreting antibody that recognized the idiotypic lambda chain but not normal lambda chains by a preliminary screen but which also reacted with idiotypic IgM from the patient's tumor cells was selected. This MoAb in fact recognized 1 in 20 X 10(3) molecules of pooled normal lambda chains, thus establishing its specificity for a private idiotypic determinant. It failed to give a detectable reaction with normal IgM, normal serum, or a panel of IgM paraproteins. The antibody bound to the patient's neoplastic B cells but not to normal tonsillar cells. The site of binding of the antibody to idiotypic IgM is clearly separate from that of another MoAb specific for idiotypic determinants on heavy plus light chains, since the two showed additive binding curves. The determinant also appeared to be less available in dimeric lambda chains than in monomeric lambda chains or in idiotypic IgM. Antibodies to idiotypic determinants on light chains show some technical advantages and should be useful for monitoring and possibly treating B cell tumors, either alone or together with the more conventional anti-idiotypic antibodies that usually recognize the heavy and light chain combination.

scholarly journals Monoclonal anti-light chain idiotype as a tumor-specific probe for human neoplastic B lymphocytes

Blood ◽  
1987 ◽  
Vol 69 (3) ◽  
pp. 919-923
Author(s):  
M Wrightham ◽  
AL Tutt ◽  
MJ Glennie ◽  
TJ Hamblin ◽  
GT Stevenson ◽  
...  
Keyword(s):  
B Cell ◽  
Tumor Cells ◽  
B Lymphocytes ◽  
Light Chain ◽  
Normal Serum ◽  
Lymphocytic Leukemia ◽  
Light Chains ◽  
Specific Probe ◽  
Tonsillar Cells ◽  
Binding Curves

Tumor cells from patients with B cell neoplasms often secrete small amounts of free monoclonal light chains that can be found in the urine. Such tumor-derived light chains of the lambda type from a patient with typical chronic lymphocytic leukemia have been used to raise mouse monoclonal antibodies (MoAbs). A hybridoma-secreting antibody that recognized the idiotypic lambda chain but not normal lambda chains by a preliminary screen but which also reacted with idiotypic IgM from the patient's tumor cells was selected. This MoAb in fact recognized 1 in 20 X 10(3) molecules of pooled normal lambda chains, thus establishing its specificity for a private idiotypic determinant. It failed to give a detectable reaction with normal IgM, normal serum, or a panel of IgM paraproteins. The antibody bound to the patient's neoplastic B cells but not to normal tonsillar cells. The site of binding of the antibody to idiotypic IgM is clearly separate from that of another MoAb specific for idiotypic determinants on heavy plus light chains, since the two showed additive binding curves. The determinant also appeared to be less available in dimeric lambda chains than in monomeric lambda chains or in idiotypic IgM. Antibodies to idiotypic determinants on light chains show some technical advantages and should be useful for monitoring and possibly treating B cell tumors, either alone or together with the more conventional anti-idiotypic antibodies that usually recognize the heavy and light chain combination.

scholarly journals Sequence diversity within a subgroup of mouse immunoglobulin kappa chains controlled by the IgK-Ef2 locus.

1981 ◽  
Vol 154 (1) ◽  
pp. 146-155 ◽  
Author(s):  
C Lazure ◽  
W T Hum ◽  
D M Gibson
Keyword(s):  
Normal Mouse ◽  
Sequence Diversity ◽  
The Other ◽  
Light Chains ◽  
Chromosome 6 ◽  
Immunoglobulin Kappa ◽  
Mouse Immunoglobulin ◽  
Complete Sequencing ◽  
Polymorphic Bands ◽  
V Region

We previously showed that a chromosome 6 locus, IgK-Ef2, controls a pair of prominent bands in normal mouse light-chain isoelectric focusing profiles. Screening of myeloma light chains derived from BALB/c mice (an IgK-EF2 alpha strain) led to the identification of seven light chains cofocusing with the polymorphic bands controlled by IgK-Ef2. Complete sequencing of the variable (V) regions of four of the light chains indicates that they are all members of the same subgroup (Vk-1A) and they differ from one another by 1--3 substitutions. One of the protein differs from the prototype V-region sequence only in the deletion of a single residue at position 95 immediately preceding of J region. The other two differ from the protype V region by 3 (two framework [fr], one complementarity-determined [cdr]) and one (fr) residues, respectively. Complete V-region sequences of two closely related light chains derived from NZB mice (an IgK-Ef2b strain) indicate the NZB proteins are derived from a distinct Vk gene (Vk-1B), differing by four substitutions from the Vk-1A sequence. The results suggest that the IgK-Ef2 polymorphism may be a result of, at least in part, the loss of the gene(s) coding for the Vk-1A subgroups in IgK-Ef2b strains of mice. The nature of the sequence diversity found in the Vk-1A subgroup indicates that either it is coded by a repeated series of virtually identical genes or that somatic mutation of a single Vk-1A gene may give rise to substitutions in framework as well as cdr regions.

scholarly journals Glycopeptides from human χ-chains

1971 ◽  
Vol 121 (2) ◽  
pp. 211-215 ◽  
Author(s):  
Celia P. Milstein ◽  
C. Milstein
Keyword(s):  
Attachment Site ◽  
Variable Region ◽  
Light Chains ◽  
Myeloma Proteins

Glycopeptides have been isolated from tryptic digests of κ-type light chains separated from human myeloma proteins obtained from the serum of two patients, Car and Rai. The glycopeptides are derived from the variable region of the chain in both cases, but from different sections. On the basis of homology it is deduced that glycopeptide from Car, κI type, is derived from position 25–31 whereas that from Rai, κII type, is from position 62–77, their sequences being respectively Ala-Ser-Gln-Asn-Ile-Ser and Phe-Ser-Gly-Ser-Gly-Ser-Gly(Thr,Asp)Phe-Thr-Leu-Asx-Ile-Ser-Arg. The significance of the results is discussed in connexion with the nature of the attachment site of carbohydrate to protein.

scholarly journals A new variable region in mouse immunoglobulin lambda light chains.

1987 ◽  
Vol 166 (1) ◽  
pp. 265-270 ◽  
Author(s):  
P Sanchez ◽  
P A Cazenave
Keyword(s):  
Light Chain ◽  
Single Injection ◽  
Gene Segment ◽  
Variable Region ◽  
Light Chains ◽  
Lambda Light Chain ◽  
Segment Sequence ◽  
Cell Clones ◽  
Mouse Immunoglobulin ◽  
Lambda Probe

A series of lambda+ murine hybridomas were derived from a BALB/c mouse after a single injection of anti-lambda 2 antibodies coupled to LPS. Nine lambda B cell clones (five lambda 2 and four lambda 3) were expected and seven reacted with antibodies specific for the C lambda 2 constant region but showed a particular isoelectric spectrum. Their RNA products did not hybridize with the V lambda probe. The partial DNA sequence of gene segments coding the unexpected light chain of one hybridoma shows that the V gene segment has only 55% homology with the V lambda 2 gene segment sequence and that J lambda 2 and probably C lambda 2 gene segments are used. Taken together, these results demonstrate the existence of a new lambda light chain.

Challenges of measuring monoclonal proteins in serum

2016 ◽  
Vol 54 (6) ◽  
Author(s):  
David F. Keren ◽  
Lee Schroeder
Keyword(s):  
Light Chain ◽  
Serum Proteins ◽  
Region Of Interest ◽  
Normal Serum ◽  
M Protein ◽  
Light Chains ◽  
Immunochemical Method ◽  
Electrophoretic Method ◽  
M Proteins ◽  
Monoclonal Proteins

AbstractThe measurement of monoclonal protein (M-protein) is vital for stratifying risk and following individuals with a variety of monoclonal gammopathies. Direct measurement of the M-protein spike by electrophoresis and immunochemical measurements of specific isotypes or free light chains pairs has provided useful information about the quantity of M-protein. Nonetheless, both traditional electrophoresis and immunochemical methods give poor quantification with M-proteins smaller than 10 g/L (1 g/dL) when in the presence of polyclonal immunoglobulins that co-migrate with the M-protein. In addition, measurements by electrophoresis of M-proteins migrating in the β- and α-regions are contaminated by normal serum proteins in those regions. The most precise electrophoretic method to date for quantification involves exclusion of the polyclonal immunoglobulins by using the tangent skimming method on electropherograms, which provides a 10-fold improvement in precision. So far, however, tangent measurements are limited to γ migrating M-proteins. Another way to improve M-protein measurements is the use of capillary electrophoresis (CE). With CE, one can employ immunosubtraction to select a region of interest in the β region thereby excluding much of the normal proteins from the M-protein measurement. Recent development of an immunochemical method distinguishing heavy/light chain pairs (separately measuring IgGK and IgGL, IgAK and IgAL, and IgMK and IgML) provides measurements that could exclude polyclonal contaminants of the same heavy chain with the uninvolved light chain type. Yet, even heavy/light results contain an immeasurable quantity of polyclonal heavy/light chains of the involved isotype. Finally, use of liquid chromatography-tandem mass spectrometry (LC-MS/MS) looms on the horizon as a means to provide more consistent and sensitive measurements of M-proteins.

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