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Results for “Germ-Line Mutation”

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PubMed1990

Clonal lymphoid progenitor cell lines expressing the BCR/ABL oncogene retain full differentiative function.

The early stages of hematopoiesis have been difficult to study due to problems in obtaining homogeneous populations of progenitor cells that retain both self-renewal and differentiative capacities. We have developed an in vitro system in which transformation of murine bone-marrow cells with the BCR/ABL oncogene, a gene associated with stem-cell leukemias, leads to the outgrowth of clonal lines that have an early lymphoid progenitor cell phenotype. The progenitor cells retain immunoglobulin heavy and light chain genes in a germ-line configuration. These cells give rise in vitro to pre-B cells that have diverse diversity-joining (D-J) region rearrangements, and on transfer to mice with severe combined immune deficiency, differentiate to surface IgM+, immunoglobulin-secreting B cells that respond to T-cell help and function in an antigen-specific fashion. Although their growth is stimulated by BCR/ABL, the progenitor cells depend for continued growth on a stromal cell-derived soluble factor distinct from the pre-B-cell growth factor, interleukin 7. These findings show that BCR/ABL can promote proliferation of an early hematopoietic progenitor cell without preventing its differentiation. This system provides a means of studying the complete B-cell developmental process from clonal progenitor cell to end-stage plasma cell.

Animals↗

PubMed1981

DNA damage as the primary cause of aging.

DNA damage appears to be ubiquitous in the biological world, as judged by the variety of organisms which have evolved DNA-repair systems. Previously, it was proposed that germ-line DNA of multicellular organisms may be protected from damage, and consequently from aging, by efficient recombinational repair during meiosis. The somatic line, however, may be vulnerable to the accumulation of DNA damage, and hence undergo aging, owing to relatively less repair. Although the DNA lesions most important in aging are not known yet, there is evidence for serveral types of endogenous damage. DNA lesions have been shown to interfere with transcription and replication, and so lead to loss of cell function and death. In mammals, there is a progressive decline of function in many different tissues with increasing age. Deterioration of central nervous system functions appears to be a critical part of the aging process. This may be due to the low DNA repair capacity which is found in postmitotic brain tissue, and which could result in the accumulation of DNA lesions in this tissue. Also reviewed is evidence that species longevity is directly related to tissue DNA-repair capacity and that aging may be accelerated by treatment with DNA-damaging agents, or in individuals with genetically defective repair. Although it has been frequently postulated that somatic mutation may be cause of aging, current evidence suggests that it is probably less important than DNA damage. A prominent theory on the evolution of aging, which attributes special importance to genes that are advantagous in youth but are deleterious later on, is discussed in terms of regulatory genes that reduce DNA repair as cells differentiate to the postmitotic state. Finally, we hypothesize that the factors which determine maximum longevity of individuals in a population are the rate of occurrence of DNA damage, the rate of DNA repair, the degree of cellular redundancy, and the extent of exposure to stress.

Aging↗

PubMed1987

Gain-of-function mutations of fem-3, a sex-determination gene in Caenorhabditis elegans.

We have isolated nine gain-of-function (gf) alleles of the sex-determination gene fem-3 as suppressors of feminizing mutations in fem-1 and fem-2. The wild-type fem-3 gene is needed for spermatogenesis in XX self-fertilizing hermaphrodites and for male development in both soma and germ line of XO animals. Loss-of-function alleles of fem-3 transform XX and XO animals into females (spermless hermaphrodites). In contrast, fem-3(gf) alleles masculinize only one tissue, the hermaphrodite germ line. Thus, XX fem-3(gf) mutant animals have a normal hermaphrodite soma, but the germ line produces a vast excess of sperm and no oocytes. All nine fem-3(gf) alleles are temperature sensitive. The temperature-sensitive period is from late L4 to early adult, a period just preceding the first signs of oogenesis. The finding of gain-of-function alleles which confer a phenotype opposite to that of loss-of-function alleles supports the idea that fem-3 plays a critical role in germ-line sex determination. Furthermore, the germ-line specificity of the fem-3(gf) mutant phenotype and the late temperature-sensitive period suggest that, in the wild-type XX hermaphrodite, fem-3 is negatively regulated so that the hermaphrodite stops making sperm and starts making oocytes. Temperature shift experiments also show that, in the germ line, sexual commitment appears to be a continuing process. Spermatogenesis can resume even after oogenesis has begun, and oogenesis can be initiated much later than normal.

Alleles↗

PubMed1988

Genetic control of sex determination in the germ line of Caenorhabditis elegans.

The nematode Caenorhabditis elegans normally exists as one of two sexes: self-fertilizing hermaphrodite or male. Development as hermaphrodite or male requires the differentiation of each tissue in a sex-specific way. In this review, I discuss the genetic control of sex determination in a single tissue of C. elegans: the germ line. Sex determination in the germ line depends on the action of two types of genes:--those that act globally in all tissues to direct male or female development and those that act only in the germ line to specify either spermatogenesis or oogenesis. First, I consider a tissue-specific sex-determining gene, fog-1, which promotes spermatogenesis in the germ line. Second, I consider the regulation of the hermaphrodite pattern of germ-line gametogenesis where first sperm and then oocytes are produced.

Animals↗

PubMed1988

The positive and negative transcriptional regulation of the Drosophila Gapdh-2 gene.

One of the genes encoding glyceraldehyde 3-phosphate dehydrogenase of Drosophila melanogaster, Gapdh-2, is expressed in all cell types examined, but its level of expression is regulated developmentally. Here we report the analysis of the regulatory sequences for the transcription of Gapdh-2. We have generated Gapdh-2-LacZ fusion genes in which the 5'-flanking sequence of Gapdh-2 has been mutated. Examination of the expression of these fusion genes, which have been introduced by transfection into the Schneider II cell line and by germ-line transformation into flies, led to the identification of two distinct regulatory regions, URS-1 and URS-2, within the first 145 bp of the 5'-flanking sequence of Gapdh-2. URS-1 activates transcription throughout the development of Drosophila. However, URS-2 exhibits a dual function during the development. It clearly represses transcription in Schneider II cells, and perhaps also in mid-stage embryos. In contrast, it activates transcription in larvae and adult flies. Thus, URS-2 plays a key role in the developmental regulation of Gapdh-2. Additionally, the efficient transcription of Gapdh-2 in larval and adult stages appears to depend on a synergistic function of URS-1 and URS-2.

Animals↗

PubMed1989

cappuccino and spire: two unique maternal-effect loci required for both the anteroposterior and dorsoventral patterns of the Drosophila embryo.

cappuccino and spire are unique Drosophila maternal-effect loci that participate in pattern formation in both the anteroposterior and dorsoventral axes of the early embryo. Mutant females produce embryos lacking pole cells, polar granules, and normal abdominal segmentation. They share these defects with the posterior group of maternal-effect genes. Although embryos are defective in abdominal segmentation, in double mutant combinations with Bicaudal D, abdominal segments can be formed in the anterior half of the egg. This indicates that embryos produced by mutant females contain the 'posterior determinant' required for abdominal segmentation (Nüsslein-Volhard et al. 1987) and suggests that the wild-type gene products are not required for production of the posterior determinant but, rather, for its localization or stabilization. The vasa protein, a component of polar granules, is not localized at the posterior pole of mutant egg chambers or embryos, providing additional support for the hypothesis that localization to or stabilization of substances at the posterior pole of the egg chamber is defective in mutant females. Females mutant for the strongest alleles also produce dorsalized embryos. Phenotypic analysis reveals that these dorsalized embryos also have abdominal segmentation defects. The mutant phenotypes can be ordered in a series of increasing severity. Pole cell formation is most sensitive to loss of functional gene products, followed by abdominal segmentation, whereas normal dorsoventral patterning is the least sensitive to loss of functional gene products. In addition, mutant females contain egg chambers that appear to be dorsalized, resulting in the production of eggs with dorsalized eggshells. Germ-line mosaics indicate that cappuccino and spire are required in the oocyte-nurse cell complex. This suggests that the eggshell phenotype results from altered pattern in the underlying germ cell. Also, we defined the epistatic relationships between several early patterning loci, on the basis of an analysis of the eggs and embryos produced by females doubly mutant for cappuccino or spire and other loci that affect the pattern of both the egg and the embryo. On the basis of our current knowledge of the genes involved in this process, we formulated a working model for the early steps in dorsoventral patterning.

Animals↗

PubMed1992

Selective disruption of genes expressed in totipotent embryonal stem cells.

Two retrovirus promoter trap vectors (U3His and U3Neo) have been used to disrupt genes expressed in totipotent murine embryonal stem (ES) cells. Selection in L-histidinol or G418 produced clones in which the coding sequences for histidinol-dehydrogenase or neomycin-phosphotransferase were fused to sequences in or near the 5' exons of expressed genes, including one in the developmentally regulated REX-1 gene. Five of seven histidinol-resistant clones and three of three G418-resistant clones generated germ-line chimeras. A total of four disrupted genes have been passed to the germ line, of which two resulted in embryonic lethalities when bred to homozygosity. The ability to screen large numbers of recombinant ES cell clones for significant mutations, both in vitro and in vivo, circumvents genetic limitations imposed by the size and long generation time of mice and will facilitate a functional analysis of the mouse genome.

Alcohol Oxidoreductases↗

PubMed1988

Insertion and excision of Caenorhabditis elegans transposable element Tc1.

The transposable element Tc1 is responsible for most spontaneous mutations that occur in Caenorhabditis elegans variety Bergerac. We investigated the genetic and molecular properties of Tc1 transposition and excision. We show that Tc1 insertion into the unc-54 myosin heavy-chain gene was strongly site specific. The DNA sequences of independent Tc1 insertion sites were similar to each other, and we present a consensus sequence for Tc1 insertion that describes these similarities. We show that Tc1 excision was usually imprecise. Tc1 excision was imprecise in both germ line and somatic cells. Imprecise excision generated novel unc-54 alleles that had amino acid substitutions, amino acid insertions, and, in certain cases, probably altered mRNA splicing. The DNA sequences remaining after Tc1 somatic excision were the same as those remaining after germ line excision, but the frequency of somatic excision was at least 1,000-fold higher than that of germ line excision. The genetic properties of Tc1 excision, combined with the DNA sequences of the resulting unc-54 alleles, demonstrated that excision was dependent on Tc1 transposition functions in both germ line and somatic cells. Somatic excision was not regulated in the same strain-specific manner as germ-line excision was. In a genetic background where Tc1 transposition and excision in the germ line was not detectable, Tc1 excision in the soma still occurred at high frequency.

Animals↗

PubMed1976

The biological origin of antibody diversity.

Antibody diversity has a compelling fascination for many scientists and over the years speculations have sometimes seemed more numerous than facts. Now the structural basis of antibody specificity is well defined. Amino acid sequences and recently three-dimensional structures of various immunoglobulins provide the most solid basis for discussing the origin of diversity. The novel pattern of variable (V) and Constant (C) regions of amino acid sequence has been resolved further to show the functional pattern of variability. Inheritance of separate V and C genes is accepted, but attempts to define more than one gene coding for each V region are considered here to be unnecessary. The pattern of variability is still best understood in terms of mutation and the presence or absence of various selective pressures. The major area of debate still hinges around the extent to which mutation and selection operate during evolution or somatically. Sequence data have now been generally interpreted to require multiple V genes carried in the germ line. A few individual VH genes have been mapped in close linkage to CH genes in the mouse. The apparent existence of three VH alleles in rabbits was a strong argument against multiple V genes. Now the three phenotypes have been shown to be due to alleles controlling the expression of three sets of VH genes all present on the same chromosome. That V-gene expression requires rejoining of V and C genes at the DNA level is now almost certain. Models for the joining process can draw on the precedents of transposable genetic elements, which are widespread in Nature. The total extent of antibody diversity remains a philosophical point. Estimates of the number of antibody molecules required for observed diversity are reduced by two recently documented proposals. Each antibody combining site apparently has many (estimated at 100) different specificities and most combinations of VH and VL regions probably form a viable site. A given combining site can be defined by its pattern of shared specificities. Several specific antibody repertoires have been measured and the size in each case is consistent with the stringency with which the specificity is selected. Repertoire size appears to be under genetic control, but there are problems in viewing the genotype through the veil of clonal selection. Molecular hybridization has been used recently in an attempt to count V and C genes directly. C genes are seen in DNA having nonreiterated sequences, as formal genetics predicts. Each V-region probe hybridizes at a similar rate to C-region probes. Interpretation of this result depends on the extent to which one V-region probe will reveal nonhomologous V genes. Previous estimates that many cross-hybridizing genes should have been seen if present are possibly exaggerated. It is argued here that the data are compatible with a germ-line gene for each probe studied. Maximum estimates for the number of germ-line genes are sufficient to account for antibody diversity...

Amino Acid Sequence↗

PubMed1993

Expression of the Sex-lethal gene is controlled at multiple levels during Drosophila oogenesis.

In addition to controlling somatic sexual development in Drosophila melanogaster, the Sex-lethal (Sxl) gene is required for proper differentiation of female germ cells. To investigate its role in germ-line development, we have examined the expression of Sxl in wild-type ovaries and ovaries that are defective in early steps of germ cell differentiation. As in the soma, the basic mechanism for on/off regulation of Sxl relies on sex-specific processing of its transcripts in germ cells. One class of female-sterile mutations, which includes fs(1)1621 and the tumorous-ovary-producing allele of the ovarian tumor gene, otu1, is defective in the splicing process. These mutants have germ lines with high amounts of Sxl RNA spliced in the male mode and a severe reduction of protein levels in the germ cells. Another class of female-sterile mutations produces a phenotype similar to that seen in fs(1)1621 and otu1 but appears to express normal levels of Sxl protein in the germ cells. However, this second class does not show the changes in protein distribution normally observed in wild-type germ cells. In the wild-type germarium, the non-differentiated germ cells show a strong cytoplasmic accumulation of Sxl protein followed, as the germ cells differentiate, by a dramatic reduction and redistribution of the protein into nuclear foci. Interestingly, two female-sterile alleles of Sxl, Sxlf4 and Sxlf5 belong to the second class, which shows persistent cytoplasmic accumulation of Sxl protein. These Sxl female-sterile mutants encode an altered protein indicating that Sxl regulates processes that eventually lead to the changes in Sxl protein distribution. Lastly, we demonstrate that during the final stages of oogenesis several mechanisms must operate to prevent the progeny from inheriting Sxl protein. Conceivably, this regulation safeguards the inadvertent activation of the Sxl autoregulatory feedback loop in the male zygote.

Animals↗

PubMed1993

Sex determination in the germ line of Drosophila melanogaster: activation of the gene Sex-lethal.

The germ line exhibits sexual dimorphism as do the somatic tissues. Cells with the 2X;2A chromosome constitution will follow the oogenic pathway and X;2A cells will develop into sperm. In both somatic and germ-line tissues, the sexual pathway chosen by the cells depends on the gene Sex-lethal (Sxl), whose function is continuously needed for female development. In the soma, the sex of the cells is autonomously determined by the X:A signal while, in the germ line, the sex is determined by cell autonomous (the X:A signal) and somatic inductive signals. Three X-linked genes have been identified, scute (sc), sisterless-a (sis-a) and runt (run), that determine the initial functional state of Sxl in the soma. Using pole cell transplantation, we have tested whether these genes are also needed to activate Sxl in the germ line. We found that germ cells simultaneously heterozygous for sc, sis-a, run and a deficiency for Sxl transplanted into wild-type female hosts develop into functional oocytes. We conclude that the genes sc, sis-a and run needed to activate Sxl in the soma seem not to be required to activate this gene in the germ line; therefore, the X:A signal would be made up by different genes in somatic and germ-line tissues. The Sxlf7M1/Sxlfc females do not have developed ovaries. We have shown that germ cells of this genotype transplanted into wild-type female hosts produce functional oocytes. We conclude that the somatic component of the gonads in Sxlf7M1/Sxlfc females is affected, and consequently germ cells do not develop.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1994

Function of Drosophila ovo+ in germ-line sex determination depends on X-chromosome number.

Germ-line sex determination in Drosophila melanogaster requires an assessment of the number of X chromosomes as measured against autosomal standards (XX = female, X = male) and signaling from the soma. Both of these sex determination cues are required for female-specific Sex-lethal+ function in germ cells. The ovo+ locus encodes zinc finger protein(s) required for female-specific splicing of Sex-lethal+ pre-mRNA, making ovo+ a candidate function acting between the two principal cues and Sex-lethal+. We have made ovo reporter genes and find that they show high activity in the germ line of females and low activity in the germ line of males. XY flies transformed into somatic females do not show high levels of reporter activity, while XX flies transformed into somatic males do. This shows that high level ovo+ expression depends on the number of X chromosomes, not the somatic sexual signals. The requirement for ovo+ function is restricted to XX flies. Mutations in ovo have no effect on XY males, X0 males or XY females, but have pronounced effects on germ cell viability in XX females, XX females with sex transformed germ lines, and XX males indicating that ovo+ gene products are required for events occurring only in flies with two X chromosomes.

Animals↗

PubMed1995

Transformation of the germ line into muscle in mes-1 mutant embryos of C. elegans.

Mutations in the maternal-effect sterile gene mes-1 cause the offspring of homozygous mutant mothers to develop into sterile adults. Lineage analysis revealed that mutant offspring are sterile because they fail to form primordial germ cells during embryogenesis. In wild-type embryos, the primordial germ cell P4 is generated via a series of four unequal stem-cell divisions of the zygote. mes-1 embryos display a premature and progressive loss of polarity in these divisions: P0 and P1 undergo apparently normal unequal divisions and cytoplasmic partitioning, but P2 (in some embryos) and P3 (in most embryos) display defects in cleavage asymmetry and fail to partition lineage-specific components to only one daughter cell. As an apparent consequence of these defects, P4 is transformed into a muscle precursor, like its somatic sister cell D, and generates up to 20 body muscle cells instead of germ cells. Our results show that the wild-type mes-1 gene participates in promoting unequal germ-line divisions and asymmetric partitioning events and thus the determination of cell fate in early C. elegans embryos.

Animals↗

PubMed1995

Mutations in the Drosophila gene bullwinkle cause the formation of abnormal eggshell structures and bicaudal embryos.

Subcellular localization of gene products and cell migration are both critical for pattern formation during development. The bullwinkle gene is required in Drosophila for disparate aspects of these processes. In females mutant at the bullwinkle locus, the follicle cells that synthesize the dorsal eggshell filaments do not migrate properly, creating short, broad structures. Mosaic analyses demonstrate that wild-type BULLWINKLE function is required in the germ line for these migrations. Since the mRNA for gurken, the putative ligand that signals dorsal follicle cell fate, is correctly localized in bullwinkle mutants, we conclude that our bullwinkle alleles do not affect the dorsoventral polarity of the oocyte and thus must be affecting the follicle cell migrations in some other way. In addition, the embryos that develop from bullwinkle mothers are bicaudal. A KINESIN:beta-GALACTOSIDASE fusion protein is correctly localized to the posterior pole of bullwinkle oocytes during stage 9. Thus, the microtubule structure of the oocyte and general transport along it do not appear to be disrupted prior to cytoplasmic streaming. Unlike other bicaudal mutants, oskar mRNA is localized correctly to the posterior pole of the oocyte at stage 10. By early embryogenesis, however, some oskar mRNA is mislocalized to the anterior pole. Consistent with the mislocalization of oskar mRNA, a fraction of the VASA protein and nanos mRNA are also mislocalized to the anterior pole of bullwinkle embryos. Mislocalization of nanos mRNA to the anterior is dependent on functional VASA protein. Although the mirror-image segmentation defects appear to result from the action of the posterior group genes, germ cells are not formed at the anterior pole. The bicaudal phenotype is also germ-line dependent for bullwinkle. We suspect that BULLWINKLE interacts with the cytoskeleton and extracellular matrix and is necessary for gene product localization and cell migration during oogenesis after stage 10a.

Animals↗

PubMed1994

Expression of N-terminally truncated cyclin B in the Drosophila larval brain leads to mitotic delay at late anaphase.

We have introduced an N-terminally truncated form of cyclin B into the Drosophila germ-line downstream of the yeast upstream activator that responds to GAL4. When such lines of flies are crossed to lines in which GAL4 is expressed in imaginal discs and larval brain, the majority of the resulting progeny die at the late pupal stage of development. Very rarely (< 0.1% of progeny) adults emerge that have a mutant phenotype typical of flies with mutations in genes required for the cell cycle; they have rough eyes, deformed wings, abnormal bristles, and die within hours of emergence. The brains of third instar larval progeny show an abnormally high proportion of mitotic cells containing overcondensed chromatids that have undergone anaphase separation, together with cells that cannot be assigned to a particular mitotic stage. Immunostaining indicates that these anaphase cells contain moderate levels of cyclin B, suggesting that persistent p34cdc2 kinase activity can prevent progression from anaphase into telophase.

Anaphase↗

PubMed1993

Identification of germ-line chimaeras by polymerase chain reaction and isoenzyme analysis of mouse spermatozoa.

In this study a rapid, simple and inexpensive procedure is described which allows potential germ-line male mice to be identified with confidence. Spermatozoa recovered by uterine washing following mating with normal female mice was analysed in two ways. First, the patterns of expression of the different isoforms of glucose phosphate isomerase were determined. Since the glucose phosphate isomerase isoforms expressed in embryo stem (ES) cell lines are frequently different from those associated with the host blastocyst, it is possible to determine the proportion of spermatozoa produced by an individual animal that was of ES cell or host-blastocyst origin. Second, DNA of spermatozoa was subjected to polymerase chain reaction (PCR) analysis using primers with specificity for the targeted mutation in the ES cells. The PCR analysis was particularly valuable in identifying germ cell chimaeras in which the contribution of ES-derived spermatozoa was significantly less than that specified by the host blastocyst.

Animals↗

PubMed1991

Influence of a V kappa 8 L chain transgene on endogenous rearrangements and the immune response to the HA(Sb) determinant on influenza virus.

A rearranged murine V kappa 8/J kappa 5 L chain gene that codes for the L chain of most antibodies generated in the primary response of BALB/c mice to the antigenic site, Sb, of the hemagglutinin (HA) molecule of influenza virus A/PR/8/34 (PR8) has been cloned. Three transgenic lines were generated by microinjecting the gene. Lines Ga and L each contain a single copy of the transgene whereas line Gb contains three complete copies. Mice of the Ga lineage showed increased V kappa 8-specific mRNA levels only in spleen, but not in nonlymphoid organs and therefore displayed apparently normal lymphoid-specific regulation of the Ig transgene. B cell hybridomas generated from these mice were analyzed for rearrangements of endogenous V kappa genes. Greater than 90% of the C kappa alleles were retained in germ-line configuration in the Ga line, compared with only 0 to 18% in the L line. Thus, a wide variation in the frequency of endogenous rearrangements is seen among mice of different lineages using the same transgene construct. None of more than 150 hybridomas derived from LPS-stimulated splenic B cells of Ga mice exhibited HA-binding activity although they expressed the transgene and, in most cases, excluded endogenous V kappa rearrangements. In contrast, a large fraction of hybridomas isolated after primary immunization with PR8 were HA(Sb)-specific. This indicated that the transgene was functional but formed HA-specific antibodies with a more restricted set of H chains than previously hypothesized. The primary anti-HA response to immunization with PR8 was diminished in all lines compared with normal mice except for a slightly accelerated but transient burst of anti-HA antibody formation in two out of three lines (Ga and Gb). This early response in G lineage mice was largely specific for HA(Sb) and thus appeared to be composed of transgene-expressing antibodies. No differences in serum titers were observed in the secondary anti-HA responses to booster inoculation with PR8 between transgenic and normal mice.

Animals↗

PubMed1991

The rheumatoid factor reactivity of a human IgG monoclonal autoantibody is encoded by a variant V kappa II L chain gene.

To determine the genetic and molecular basis for rheumatoid factor (RF) autoantibody reactivity in patients with destructive, erosive arthritis, we established a human lymphoblastoid cell line (hRF-1) from a patient with polyarthritis that produced an IgG RF mAb, mAb hRF-1. Studies of isolated H and L chains showed that the specificity of RF reactivity is conferred by mAb hRF-1 L chains. The L chain gene was cloned from a cDNA library prepared from hRF-1 cells. The nucleotide sequence was similar to known V kappa II L chains except for a two nucleotide change corresponding to a change of two amino acids in an invariable region of FR3. A germ-line gene with one of the nucleotide changes was identified by polymerase chain reaction in multiple cell lines, including K562 that does not rearrange Ig genes, but the other nucleotide change appeared to be due to mutation. Either or both of these amino acid changes may contribute to the RF reactivity, because an antibody with the same V kappa II L chain except for these two amino acid changes in FR3 did not have RF reactivity. The RF reactivity of isolated L chains from mAb hRF-1 was confirmed by transfecting COS cells with an expression vector encoding the hRF-1 kappa-chain and showing that the secreted k-chains had RF reactivity. Expression of this variant V kappa II L chain gene may form the basis for RF autoantibody reactivity in some patients.

Amino Acid Sequence↗