RESUMEN
Sheep is the representative of the artiodactyla and is an agriculturally important animal, but limited knowledge is available with regard to its immunoglobulin genes and their expression mechanisms in the sheep. Based on the recently released sheep genome, we have characterized the genomic organization of the sheep immunoglobulin light gene loci. The sheep Igλ locus, located on chromosome 17, contains 2Cλ segments each preceded by a Jλ, but the Cλ2 appears to be a pseudogene. A total of 42 Vλ segments (14 potentially functional genes, 1 ORF and 27 pseudogenes) were identified. In contrast, the Igκ locus on chromosome 3 contains only a single Cκ gene, 3 Jk segments and 13 Vκ segments (8 potentially functional genes and 5 pseudogenes). Analysis of junctions of the recombined VJ transcripts revealed a restricted Vλ4-Jλ1-Cλ1 recombination and Vk6-Jk3-Cκ recombination, respectively encode most of λ and κ chain antibody repertoire in the sheep despite more potential germline encoded combinatorial diversity. Therefore, the sheep may use gene conversion in combination with somatic hypermutation for antibody repertoire formation.
Asunto(s)
Genes de las Cadenas Ligeras de las Inmunoglobulinas/genética , Genoma/genética , Cadenas kappa de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/genética , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Mapeo Cromosómico , Cromosomas de los Mamíferos/genética , Cadenas kappa de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/clasificación , Datos de Secuencia Molecular , Filogenia , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido Nucleico , OvinosRESUMEN
The specific organ placenta is much more than a filter: it is an organ that protects, feeds and regulates the growth of the embryo. Affinity chromatography, ELISA, SDS-PAGE and matrix-assisted laser desorption ionization mass spectrometry were used. Using 10 intact human placentas deprived of blood, a quantitative analysis of average relative content [% of total immunoglobulins (Igs)] was carried out for the first time: (92.7), IgA (2.4), IgM (2.5), kappa-antibodies (51.4), lambda-antibodies (48.6), IgG1 (47.0), IgG2 (39.5), IgG3 (8.8) and IgG4 (4.3). It was shown for the first time that placenta contains sIgA (2.5%). In the classic paradigm, Igs represent products of clonal B-cell populations, each producing antibodies recognizing a single antigen. There is a common belief that IgGs in mammalian biological fluids are monovalent molecules having stable structures and two identical antigen-binding sites. However, similarly to human milk Igs, placenta antibodies undergo extensive half-molecule exchange and the IgG pool consists of 43.5 ± 15.0% kappa-kappa-IgGs and 41.6 ± 17.0% lambda-lambda-IgGs, while 15.0 ± 4.0% of the IgGs contained both kappa- and lambda-light chains. Kappa-kappa-IgGs and lambda-lambda-IgGs contained, respectively (%): IgG1 (47.7 and 34.4), IgG2 (36.3 and 44.5), IgG3 (7.4 and 11.8) and IgG4 (7.5 and 9.1), while chimeric kappa-lambda-IgGs consisted of (%): 43.5 IgG1, 41.0 IgG2, 5.6 IgG3 and 7.9 IgG4. Our data are indicative of the possibility of half-molecule exchange between placenta IgGs of various subclasses, raised against different antigens, which explains a very well-known polyspecificity and cross-reactivity of different human IgGs.
Asunto(s)
Inmunoglobulina G/inmunología , Placenta/inmunología , Linfocitos B/inmunología , Reacciones Cruzadas , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina A Secretora/análisis , Inmunoglobulina A Secretora/clasificación , Inmunoglobulina A Secretora/inmunología , Inmunoglobulina G/análisis , Inmunoglobulina G/clasificación , Cadenas Ligeras de Inmunoglobulina/inmunología , Cadenas kappa de Inmunoglobulina/inmunología , Cadenas lambda de Inmunoglobulina/análisis , Cadenas lambda de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/inmunología , EmbarazoRESUMEN
Naturally occurring antibody repertoires of cattle (Bos taurus) include a group of IgMlambda antibodies with exceptionally long complementarity-determining region 3 of the heavy chain (CDR3H) segments, containing multiple Cys residues. These massive CDR3H segments will greatly influence the tertiary and quaternary structures of the bovine IgM combining sites. As an antibody's combining site is formed by both heavy and light chains, we have analyzed the nucleotide sequences and structural properties of the lambda-light chains that pair with micro -heavy chains containing exceptionally long CDR3H. There appears to be an exquisite selective pressure for the use of three V(lambda)1 genes (V(lambda)1x and two new V(lambda)1d and V(lambda)1e genes) in IgM with unusually long CDR3H. The V(lambda)1d and V(lambda)1e genes are similar to each other, but diverge from the other V(lambda)1 genes into two closely related subfamilies. The available bovine V(lambda) genes are classified into three V(lambda) gene families: V(lambda)1, V(lambda)2 and V(lambda)3 based on nucleotide similarity >/=80%. Further, analysis of total Ser content and positions of Ser residues in the sequences was found to be sufficient to classify the cattle V(lambda)1 subfamilies. Patterns of Ser residues differ for V(lambda) domains from ruminant species (e.g. cattle, sheep and goats) and other mammals (e.g. humans and mice). These 'Ser signatures' can be used to track divergent evolution in lambda-light chains. Interestingly, Ser90L in complementarity-determining region 3 of the light chain (CDR3L) occurred in all V(lambda) domains that pair with V(H) regions containing exceptionally long CDR3H. A structural role for Ser90L was revealed in homology models of V(lambda) domains, i.e. to hold the ascending polypeptide of CDR3L in a relatively tight space between the N-terminal segment and residues from CDR1L. The CDR3L of V(lambda) domains also occupied smaller volumes if paired to V(H) domains with extremely long CDR3H (>/=48 residues), and were more variable in their conformation and filled larger volumes if CDR3Hs were
Asunto(s)
Bovinos/inmunología , Regiones Determinantes de Complementariedad/química , Cadenas Pesadas de Inmunoglobulina/química , Inmunoglobulina M/química , Cadenas lambda de Inmunoglobulina/química , Secuencia de Aminoácidos , Animales , Linfocitos B/inmunología , Secuencia de Bases , Regiones Determinantes de Complementariedad/genética , Expresión Génica , Genes de Inmunoglobulinas , Humanos , Cadenas Pesadas de Inmunoglobulina/genética , Inmunoglobulina M/genética , Inmunoglobulina M/inmunología , Región Variable de Inmunoglobulina/química , Región Variable de Inmunoglobulina/clasificación , Región Variable de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/genética , Modelos Inmunológicos , Datos de Secuencia Molecular , Familia de Multigenes , Filogenia , Alineación de Secuencia , Serina/químicaRESUMEN
The combinatorial immune response is restricted to jawed vertebrates with cartilaginous fishes being the lowest extant species to have the mechanism for diversification and an extensive panoply of immunoglobulins, T-cell receptors and MHC products. Here, we review the molecular events of the "big bang" or rapid evolutionary appearance of the functionally complete combinatorial immune system coincident with the appearance of ancestral jawed vertebrates, suggesting that this event was catalyzed by horizontal transfer of DNA processing systems. We analyze the nature and extent of variable and constant domain diversity among the distinct immunoglobulin sets of carcharhine sharks focusing upon the lambda-like light chains and the mu and omega heavy chains. The detection and isolation of natural antibodies from the blood of unimmunized sharks illustrates a surprising range of recognition specificities and the existence of polyspecificity suggests that the antibody-forming system of sharks offers unique opportunities for studies of immunological regulation. Although the homologies between shark and mammalian immunoglobulins are unequivocal, major differences in segmental gene organization present challenges to our understanding of basic immunological phenomena such as clonal restriction.
Asunto(s)
Evolución Molecular , Cadenas Pesadas de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/genética , Tiburones/genética , Secuencia de Aminoácidos , Animales , Anticuerpos/genética , Anticuerpos/inmunología , Antígenos/inmunología , Humanos , Inmunidad , Regiones Constantes de Inmunoglobulina/clasificación , Regiones Constantes de Inmunoglobulina/genética , Regiones Constantes de Inmunoglobulina/inmunología , Cadenas Pesadas de Inmunoglobulina/clasificación , Cadenas Pesadas de Inmunoglobulina/inmunología , Región Variable de Inmunoglobulina/clasificación , Región Variable de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/inmunología , Cadenas lambda de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/inmunología , Datos de Secuencia Molecular , Tiburones/inmunologíaRESUMEN
Sequence diversity in the human antibody repertoire is generated in two steps: by the combinatorial assembly of V gene segments and by somatic hypermutation. Here, we have characterised these processes for the lambda (lambda) light chain using a library of 7600 lambda cDNA clones from peripheral blood lymphocytes. By hybridisation and sequencing we found that most lambda chains are derived from the cluster of V(lambda) segments closest to the J(lambda)-C(lambda) pairs and that there is considerable variation in the use of individual V(lambda) segments (ranging from 0.02% to 27%): three of the 30 functional V(lambda) segments encode half the expressed V(lambda) repertoire. As a result of these biases, sequence diversity in the primary repertoire is focused at the centre of the antigen binding site. By contrast, somatic hypermutation spreads diversity to the periphery. Comparison with the human kappa (kappa) light chain indicates that both kappa and lambda use the same strategy for searching sequence space and have almost identical patterns of diversity in the mature antibody repertoire.
Asunto(s)
Variación Genética , Región Variable de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/genética , Frecuencia de los Genes , Humanos , Región Variable de Inmunoglobulina/química , Región Variable de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/química , Cadenas lambda de Inmunoglobulina/clasificación , Linfocitos/fisiología , Modelos Genéticos , Modelos Moleculares , Conformación Proteica , Análisis de Secuencia de ADNRESUMEN
Primary localized amyloidosis has been described in many different organs in the body. Studies by immunohistochemical techniques have suggested an immunoglobulin light chain origin of the amyloid material. Only in a limited number of cases has the amyloid protein been characterized by amino acid sequence analysis as subtypes of immunoglobulin light chain or heavy chain. In this report, two cases of primary localized amyloidosis of the eyelid are presented. The amyloid substance has been extracted and a major fibril protein subjected to amino acid sequence analysis. Both amyloid proteins were part of the variable region of immunoglobulin light chains, subtype lambda V and subtype lambda VI, respectively. While lambda VI has been shown to be a common subtype in systemic immunoglobulin light chain-amyloidosis, it has never been demonstrated in localized amyloid. Very few lambda V immunoglobulin light chains have been characterized and the subgroup has never been found in amyloid before.
Asunto(s)
Amiloide/inmunología , Amiloidosis/inmunología , Enfermedades de los Párpados/inmunología , Párpados/inmunología , Región Variable de Inmunoglobulina/análisis , Cadenas lambda de Inmunoglobulina/análisis , Anciano , Secuencia de Aminoácidos , Amiloide/aislamiento & purificación , Amiloidosis/patología , Electroforesis en Gel de Poliacrilamida , Enfermedades de los Párpados/patología , Párpados/química , Párpados/patología , Femenino , Humanos , Cadenas lambda de Inmunoglobulina/clasificación , Persona de Mediana Edad , Datos de Secuencia MolecularRESUMEN
We recently completed a map of the human immunoglobulin lambda (IGL) locus on chromosome 22q11.2 and showed that the V lambda genes are arranged in three distinct clusters, each containing members of different V lambda families. We have now sequenced each of these V lambda genes and determined which are functional by comparison with the expressed repertoire. Our analysis indicates that there are approximately 30 functional V lambda genes, depending on the haplotype, that belong to ten V lambda families (five V lambda 1, five V lambda 2, eight V lambda 3, three V lambda 4, three V lambda 5, one V lambda 6, two V lambda 7, one V lambda 8, one V lambda 9 and one V lambda 10). V lambda genes related to the major human V lambda families (V lambda 1, V lambda 2 and V lambda 3) predominate in species that express mainly lambda light chains.
Asunto(s)
Región Variable de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/genética , Secuencia de Aminoácidos , Secuencia de Bases , ADN , Evolución Molecular , Células Germinativas , Humanos , Región Variable de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/clasificación , Datos de Secuencia Molecular , Filogenia , Homología de Secuencia de Aminoácido , Homología de Secuencia de Ácido NucleicoRESUMEN
The C region of human lambda L chains is specified by multiple C lambda genes of which three--C lambda 1, C lambda 2, and C lambda 3--encode for the isotypes designated Mcg+, Kern- Oz-, and Kern- Oz+, respectively. The Mcg, Kern, and Oz factors have been characterized by sequence differences involving specific C lambda amino acid residues. They have also been recognized serologically by polyclonal antisera but, with rare exception, these reagents are no longer available. We have obtained two murine anti-human lambda-chain mAb, 14G1 and 14D1, that recognize antigenic determinants specific for the C lambda isotypes Mcg and Oz, respectively. These antisera have been used to classify as Mcg+/Mcg- or Oz+/Oz- monoclonal lambda-chains (Bence Jones proteins) and intact Ig lambda proteins. There was complete concordance between the chemical and serologic assignment of lambda-chains as Mcg+/Mcg- or as Oz+/Oz-; no single protein expressed both isotypes. There was no evident association between the C region isotype Mcg or Oz and the V region subgroup of the protein tested. However, our finding that four of seven amyloid-associated lambda VI Bence Jones proteins were Oz+ suggests a predominant expression of the C lambda 3 gene product among proteins of this uncommon V lambda subgroup.
Asunto(s)
Anticuerpos Monoclonales , Epítopos/inmunología , Regiones Constantes de Inmunoglobulina/clasificación , Isotipos de Inmunoglobulinas/clasificación , Cadenas lambda de Inmunoglobulina/clasificación , Animales , Especificidad de Anticuerpos , Genotipo , Humanos , Regiones Constantes de Inmunoglobulina/genética , Regiones Constantes de Inmunoglobulina/inmunología , Isotipos de Inmunoglobulinas/genética , Isotipos de Inmunoglobulinas/inmunología , Cadenas lambda de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/inmunología , Ratones , Ratones Endogámicos BALB CRESUMEN
The availability of numerous antisera prepared against lambda-type Bence Jones proteins and lambda chains of known amino acid sequence has led to the differentiation and classification of human lambda light chains into one of five V lambda subgroups. The five serologically defined subgroups, V lambda I, V lambda II, V lambda III, V lambda IV, and V lambda VI, correspond to the chemical classification that is based on sequence homologies in the first framework region (FR1). Proteins designated by sequence as lambda V react with specific anti-lambda II antisera and are thus included in the V lambda II subgroup classification. The isotypic nature of the five V lambda subgroups was evidenced through analyses of lambda-type light chains that were isolated from the IgG of normal individuals. Based on analyses of 116 Bence Jones proteins, the frequency of distribution of the lambda I, lambda II/V, lambda III, lambda IV, and lambda VI proteins in the normal lambda chain population is estimated to be 27%, 37%, 23%, 3%, and 10%, respectively. This distribution of V lambda subgroups was comparable to that found among 82 monoclonal Ig lambda proteins. Considerable V lambda intragroup antigenic heterogeneity was also apparent. At least two sub-subgroups were identified among each of the five major V lambda subgroups, implying the existence of multiple genes in the human V lambda genome. The V lambda classification of 54 Ig lambda proteins obtained from patients with primary or multiple myeloma-associated amyloidosis substantiated the preferential association of lambda VI light chains with amyloidosis AL and the predominance of the normally rare V lambda VI subgroup in this disease.
Asunto(s)
Región Variable de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/clasificación , Amiloidosis/etiología , Amiloidosis/inmunología , Anticuerpos Monoclonales/genética , Anticuerpos Monoclonales/inmunología , Proteína de Bence Jones/genética , Proteína de Bence Jones/inmunología , Humanos , Sueros Inmunes , Inmunodifusión , Regiones Constantes de Inmunoglobulina/genética , Regiones Constantes de Inmunoglobulina/inmunología , Inmunoglobulina G/genética , Inmunoglobulina G/inmunología , Región Variable de Inmunoglobulina/genética , Región Variable de Inmunoglobulina/inmunología , Cadenas lambda de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/inmunología , Mieloma Múltiple/complicaciones , Mieloma Múltiple/inmunología , Proteínas de Mieloma/genética , Proteínas de Mieloma/inmunologíaRESUMEN
Three new human lambda L chain-like Ig genes are identified by restriction enzyme and nucleotide sequence analysis. Two genes, 14.1 and 16.1, have intact J and C regions, and are potentially functional, with open reading frames. A third gene, 18.1, is a pseudogene. The evolutionary lineage of these genes compared to the known functional locus lambda C1-lambda C6 can be surmised from Southern blot and nucleotide homologies. This study demonstrates that the human lambda gene family is more complex than previously recognized.
Asunto(s)
Genes , Cadenas Ligeras de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/genética , Secuencia de Aminoácidos , Secuencia de Bases , Cromosomas Humanos 21-22 e Y , ADN/genética , Enzimas de Restricción del ADN , Humanos , Regiones Constantes de Inmunoglobulina/genética , Cadenas J de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/clasificación , Homología de Secuencia de Ácido NucleicoRESUMEN
Of 94 hairy cell leukemia (HCL) patients studied for immunologic phenotype of their hairy cells, 89 patients had B cell markers and five patients were both surface immunoglobulin (slg) negative and E rosette negative. Forty of the 77 cases that had the heavy chains individually determined had IgG only (52.0%); 23 others had IgG in addition to other Ig heavy chains. Seventy-nine patients had monoclonal light chains; 65 with kappa chain and 14 with lambda chain. The only significant difference with respect to survival among the various slg groups occurred between the kappa chain and the lambda chain groups. Within the first 46 months after diagnosis of HCL, 20 deaths occurred among the 65 kappa chain patients, whereas the first and only death among the lambda chain patients occurred at 68 months after diagnosis. The only clinical or laboratory parameter that was significantly different between these two immunologic subgroups was the incidence of infections. Among the lambda chain patients, an infectious complication rate of 28.6% was observed subsequent to the diagnosis of HCL, whereas this rate was 68.8% in kappa chain patients (P = .005). The survival of lambda patients was found to exceed that of the kappa patients by the generalized Wilcoxon test (P = .03). However, when the log rank test was used, no significant difference was detected (P = .13).
Asunto(s)
Leucemia de Células Pilosas/mortalidad , Humanos , Cadenas kappa de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/clasificación , Leucemia de Células Pilosas/genética , Fenotipo , Pronóstico , Receptores de Antígenos de Linfocitos B/clasificaciónRESUMEN
Inbred mouse make 3 lambda chain subtypes. The lambda 1 and lambda 3 chains have similar variable (V) regions (in both the same V gene segment [V lambda 1] is used), whereas lambda 2 and lambda 3 have similar constant (C) regions. Despite the lambda 1 and lambda 3 V region similarity, lambda 1 occurs much more frequently than lambda 3 (and lambda 2) in the serum immunoglobulins and antibody responses of most inbred strains of mice. To explore the basis for the lambda 1 predominance, we compared the rates of synthesis of the 3 subtypes and the frequencies of the B cells that synthesize them, focussing on "resting" (i.e., unstimulated) and on polyclonally stimulated B cells from spleens of unimmunized BALB/c mice. In resting cells the relative rates of synthesis and the relative frequencies of the respective B cells were in accord, indicating that the rate of lambda chain synthesis is approximately the same per resting B cell, regardless of the lambda subtype it produces. However, in the polyclonally stimulated cells, lambda 1 was made 7 times faster than lambda 2 and 10 times faster than lambda 3; normalizing these rates by the frequencies of the respective stimulated cells suggests that in stimulated B cells lambda 1 chains are made 5 times faster per cell than lambda 2 or lambda 3, while the latter are made at about the same rate per cell. In view of the marked structural homology between lambda 2 and lambda 3 genes in segments other than the V-gene segment, we suggest that the pronounced differences among polyclonally stimulated B cells in expression of the genes for the various lambda subtypes may be due to the presence of less potent enhancer-like sequences in the lambda 2 and lambda 3 genes than in the lambda 1 gene.
Asunto(s)
Linfocitos B/inmunología , Cadenas Ligeras de Inmunoglobulina/biosíntesis , Cadenas lambda de Inmunoglobulina/biosíntesis , Activación de Linfocitos , Animales , Concanavalina A/farmacología , Cadenas Pesadas de Inmunoglobulina/análisis , Cadenas lambda de Inmunoglobulina/análisis , Cadenas lambda de Inmunoglobulina/clasificación , Cinética , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos , Receptores de Antígenos de Linfocitos B/análisis , Tunicamicina/farmacologíaRESUMEN
Several inbred or partially inbred mouse strains derived from wild mice of different Mus subgroups were surveyed for expression of lambda 1 light chain. One strain, SPE, expressed little or no lambda 1 chains. Two populations of antibodies were obtained by immunization of SPE mice with lambda 1 light chain isolated from the BALB/c J558 (alpha, lambda 1) myeloma protein. One population of antibodies recognized lambda 1 allotypic determinants located on the C terminal fragment beginning at the residue 176. A second population was directed against epitopes present on both lambda 1 and lambda 3 chains. These determinants, which were detected in all strains tested with the exception of SPE, were located in the V region. This result is in concordance with recent DNA studies showing that the lambda 1 and lambda 3 isotype use the same V lambda 1 genes (Blomberg, B. et al., Proc. Natl. Acad. Sci. USA 1981. 78: 3765). Whether the V epitopes recognized by SPE antibodies are allotypic or isotypic in nature is not certain.
Asunto(s)
Cadenas Ligeras de Inmunoglobulina/genética , Cadenas lambda de Inmunoglobulina/genética , Ratones Endogámicos/inmunología , Muridae/inmunología , Polimorfismo Genético , Animales , Anticuerpos Antiidiotipos/análisis , Unión Competitiva , Epítopos/análisis , Sueros Inmunes/análisis , Alotipos de Inmunoglobulinas/análisis , Cadenas lambda de Inmunoglobulina/clasificación , Cadenas lambda de Inmunoglobulina/inmunología , Ratones , Ratones Endogámicos BALB CRESUMEN
To determine whether the infrequency of immunoglobulins with lambda 3 light chains is due to a corresponding scarcity of lambda 3 B cells, the production of the various lambda chain subtypes (lambda 1, lambda 2, and lambda 3) by normal spleen cells was compared. The results showed that lambda 1, lambda 2, and lambda 3 chains are produced in a ratio of about 1.0: 0.7 : 0.3, respectively. The argument is made that lambda 1, lambda 2, and lambda 3 B cells exist in the same ratio. Results obtained with neonatal and nude mouse spleen cells suggest that these small differences are not due to stimulatory effects of environmental antigens or regulatory T cells. The much greater disparity in the abundance of lambda subtypes in various antibody responses and serum Ig suggests that lambda 1 B cells may be more likely than lambda 2 or lambda 3 B cells to differentiate into antibody-secreting plasma cells.
Asunto(s)
Células Productoras de Anticuerpos/inmunología , Linfocitos B/inmunología , Cadenas Ligeras de Inmunoglobulina/biosíntesis , Cadenas lambda de Inmunoglobulina/biosíntesis , Bazo/inmunología , Animales , Animales Recién Nacidos , Células Productoras de Anticuerpos/citología , Linfocitos B/citología , Diferenciación Celular , Electroforesis en Gel de Poliacrilamida , Cadenas lambda de Inmunoglobulina/análisis , Cadenas lambda de Inmunoglobulina/clasificación , Técnicas de Inmunoadsorción , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Desnudos , Bazo/citologíaRESUMEN
Nine human antibodies to factor VIII were isolated from haemophilic plasmas by affinity chromatography and gel filtration and six were subsequently subjected to immunological characterization. Three partially purified preparations were similarly characterized. Eight of the antibodies were characterized as being exclusively IgG and one preparation was found to contain IgM. Seven of the antibodies contained only a single light chain type, four being of type lambda and three of type kappa. Two antibody preparations contained both kappa and lambda light chains. In four of the preparations, only a single heavy chain sub-class could be demonstrated, three of IgG3 and one of IgG4. Of the remainder, three were a mixture of IgG3 and IgG4 sub-classes and one contained both IgG2 and IgG4. IgG sub-classification could not be achieved with the IgM-containing preparation. These results demonstrate a restricted heterogeneity of light and heavy chains in human antibodies to factor VIII.