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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The B cell lymphoma I.29 consists of a mixture of cells expressing membrane-bound immunoglobulin M (IgM) (lambda) and IgA (lambda) of identical idiotypes. Whereas most of the cells express either IgM or IgA alone, 1 to 5% of the cells in this tumor express IgM and IgA simultaneously within the cytoplasm and on the cell membrane (R. Sitia et al., J. Immunol. 127:1388-1394, 1981; R. Sitia, unpublished data). When IgM+ cells are purified from the lymphoma and passaged in mice or cultured, a portion of the cells convert to IgA+. These properties suggest that some cells of the I.29 lymphoma may undergo immunoglobulin heavy chain switching, although it is also possible that the mixed population was derived by a prior switching event in a clone of cells. We performed Southern blotting experiments on genomic DNAs isolated from populations of I.29 cells containing variable proportions of IgM+ and IgA+ cells and on a number of cell lines derived from the lymphoma. The results were consistent with the deletion model for heavy chain switching, as the IgM+ cells contained rearranged mu genes and alpha genes in the germ line configuration on both the expressed and nonexpressed heavy chain chromosomes, whereas the IgA+ cells had deleted both mu genes and contained one rearranged and one germ line alpha gene. In addition, segments of DNA located within the intervening sequence 5' to the mu gene, near the site of switch recombination, were deleted from both the expressed and the nonexpressed chromosomes. Although mu genes were deleted from both chromosomes in the IgA+ cells, the sites of DNA recombination differed on the two chromosomes. On the expressed chromosome, Smu sequences were recombined with S alpha sequences, whereas on the nonexpressed chromosome, Smu sequences were recombined with S gamma 3 sequences.
Mol Cell Biol 1982 Aug
PMID:Rearrangements and deletions of immunoglobulin heavy chain genes in the double-producing B cell lymphoma I.29. 629 Aug 69

The induction of immune responses to orally-administered trinitrophenyl (TNP)-haptenated Streptococcus mutans or its cell wall components and enhancement of immune responses with oral adjuvants has been studied in high IgA responsive C3H/HeJ mice and in gnotobiotic rats. Gastric intubation of TNP-S. mutans to LPS non-responsive C3H/HeJ or syngeneic, LPS responsive C3H/HeN mice induced IgA responses as determined by measuring splenic plaque-forming cell (PFC) responses and IgA anti-TNP antibodies in serum, saliva, and urine. Higher IgA responses always occurred in C3H/HeJ mice given oral S. mutans antigen than similarly treated C3H/HeN animals. Oral administration of the adjuvants concanavalin A or S. mutans cell wall peptidoglycan (PG) with antigen resulted in augmented IgA responses, especially in C3H/HeJ mice. On the other hand, oral administration of muramyl dipeptide (MDP) with antigen boosted anti-TNP responses in C3H/HeN, but not in C3H/HeJ, mice. Gnotobiotic rats given S. mutans whole cells (WC) or purified cell walls (CW) by the oral route exhibited a salivary IgA immune response which was potentiated greater than twofold when antigen was given with PG or MDP. In other studies, S. mutans WC or CW antigen in water-oil-water (W/O/W) emulsion or liposomes was administered by gastric intubation to rats. Significant salivary IgA responses were induced with these antigen-adjuvant preparations. Although rats given S. mutans WC or CW were protected from S. mutans challenge, the greatest degree of caries immunity was obtained in animals which received antigen and adjuvant and which exhibited significant salivary IgA antibody levels. In preliminary studies, it was observed that local injection of rats in the salivary gland region with a ribosomal preparation from S. mutans resulted in a significant salivary IgA response and caries immunity. The potential for soluble and lipid carrier adjuvants in oral vaccines for induction of protective antibodies to S. mutans is discussed.
Mol Immunol 1983 Sep
PMID:Oral adjuvants enhance IgA responses to Streptococcus mutans. 635 63

Microbial IgA proteases cleave human serum IgA1 immunoglobulin, but human secretory IgA is resistant to hydrolysis. We have found this resistance to be due to an inhibition of protease activity that is mediated by the Fab region of secretory IgA. The IgA proteases of the genus Neisseria are more sensitive to inhibition than is the protease of Streptococcus sanguis. There is also a serum inhibitor of Neisseria proteases that co-chromatographs with IgG. Monoclonal (myeloma) human IgG proteins and plasma protease inhibitors such as alpha-1-antitrypsin and alpha-2-macroglobulin do not inhibit. Human sera do not contain inhibitor to S. sanguis protease activity. We conclude that microbial IgA proteases are subject to inhibition by IgA in secretions and IgG in serum, and this activity is most consistent with being an anti-enzyme antibody. The insensitivity of S. sanguis IgA protease to inhibition is unexplained but provides further evidence that the IgA proteases are structurally diverse.
Mol Immunol 1983 Sep
PMID:Inhibition of microbial IgA proteases by human secretory IgA and serum. 641 73

J-chain staining of IgA- and IgM-producing immunocytes was significantly enhanced when tissue sections were pretreated with acid urea, apparently because molecular unfolding exposed concealed J-chains. This indicated substantial completion of the Ig polymers at the cytoplasmic level, which was verified by diffuse binding of SC in vitro to the cytoplasm of most J-chain-positive IgA and IgM cells. This process involved specific non-covalent forces which showed the same interrelation as that noted for isolated dimeric IgA and 19S IgM--the latter as well as IgM cells exhibiting stronger binding of SC than the IgA counterparts. Conversely, J-chain staining of IgD and IgG immunocytes was not enhanced by acid urea and these cells did not generally express affinity for SC; rare exceptions could apparently be ascribed to artifacts or dual isotype production including IgA or IgM polymers. Parallel demonstration of J-chain and SC binding seems to be the best available method for studies of polymer-producing immunocyte populations and offers the advantage of in situ evaluation of cell distribution in relation to morphology. The reliability of this approach was attested to by the fact that IgA immunocytes in all secretory tissues investigated (salivary, mammary and lacrimal glands; nasal and intestinal mucosae) expressed J-chain (87-97%) and SC affinity (84-87%) in comparable proportions, indicating that almost 90% of the cells were engaged mainly in dimer production. The observation that most IgD and 50-70% of the IgG immunocytes in secretory tissues expressed J-chain, has implications for the differentiation of B-cell clones homing to such sites. Conversely, IgG cells in extra-glandular tissues showed strikingly reduced J-chain production and such sites contained IgA immunocytes with heterogeneous expression of J-chain and SC affinity. Thus, in the extra-follicular area of palatine tonsils 70-80% of the IgA cells seemed to be pure monomer producers and the remainders apparently generated a mixed product. Most immunocytes in extra-glandular tissues may therefore belong to mature clones with completely or partially repressed J-chain synthesis.
Mol Immunol 1983 Sep
PMID:Immunohistochemical characterization of intracellular J-chain and binding site for secretory component (SC) in human immunoglobulin (Ig)-producing cells. 641 74

The relationship between synthesis, secretion, and subcellular localization of J-chain, IgM, IgA, and IgG was investigated in cultures of PWM-stimulated human PBL and in lymphoblastoid cell lines. Cells were examined for surface, cytoplasmic, and secreted immunoglobulins (Igs) and J-chain by immunofluorescence and radioimmunoassay (RIA). By these techniques, J-chain was detected in cells that produce polymeric or monomeric Igs. In PWM-stimulated PBL the synthesis of J-chain paralleled the production of Igs. In both PWM-stimulated (for 2 days) and unstimulated PBL, equal proportions of free and disulfide-linked J-chain were found. Increased amounts of intracellular J-chain were produced at later stages in PWM-stimulated PBL and J-chain occurred mostly in a free form. In tissue culture fluids, J-chain was not secreted in a free form but was always disulfide-linked to polymeric Igs. In lymphoblastoid cell lines, J-chain was present in a disulfide-linked form in IgM and IGA producers, but in IgG cells and in an IgM cell line (DAUDI) that did not secrete IgM but expressed it on the cell membrane, intracellular J-chain was present in free form. Although various proportions of polymeric and monomeric IgA were seen in culture fluids from IgA-secreting cell lines, intracellular IgA occurred mostly in a monomeric form. Further studies revealed that the ability to produce polymers was not equally distributed among all cells and might vary according to their content of J-chain and stage of maturation. Subcellular fractionation and subsequent analyses for J-chain and Ig in PWM-stimulated PBL and in IgM or IgG-producing cell lines revealed that these proteins were associated with fractions that contained ribosomes, cell sap, and low molecular weight RNA. In lysates of IgG and J-chain producing cells grown in the presence of 3H-labeled amino acids, intracellular J-chain was not disulfide-linked to IgG.
Mol Immunol 1983 Sep
PMID:Biosynthesis of J-chain in human lymphoid cells producing immunoglobulins of various isotypes. 641 75

The molecular basis for the two different forms of IgA in mice, distinguished by the covalent or non-covalent association of light (L) and heavy (H) chains, is unknown. In this communication, we show, using somatic cell hybridization to construct cells producing new combinations of alpha and L chains, that individual L chains probably can pair both covalently and non-covalently depending on the alpha chain.
Mol Immunol 1984 Sep
PMID:IgA polymorphism in mice: individual light chains can pair covalently with some alpha heavy chains and non-covalently with others. 643 42

Both subclasses of human polymeric IgA (pIgA) were selectively transported from the serum into the bile of mice relative to human IgG or IgM. Removal of human pIgA from serum corresponded to the clearance kinetics shown for murine pIgA. The biliary pIgA was intact as determined by sucrose density gradient ultracentrifugation. This hepatic uptake was specific for the IgA isotype and occurred independently of receptors in the liver specific for glycoproteins that terminate with galactose or mannose moieties. Desialylation of human pIgA resulted in its rapid clearance from serum and subsequent deposition in the liver in a manner similar to most other desialylated serum glycoproteins. The desialylated pIgA present in bile was also an intact molecule; thus the asialoglycoprotein receptor may represent an additional mechanism for the transport of serum pIgA into bile.
Mol Immunol 1984 Oct
PMID:Selective hepatobiliary transport of human polymeric IgA in mice. 650 51

The relationship between the pathways of B cell differentiation leading to IgE or IgA expression was analyzed by assessing the isotype potential of primed B cells as revealed over many generations of clonal outgrowth in splenic fragment cultures. Cells from (CBA/N X BALB/C) F1 male and female mice primed with phosphocholine (PC)-hemocyanin (Hy) and given a secondary stimulus with PC-Hy or PC-determinants via an Ascaris infection gave rise to a large proportion (25-48%) of clones which expressed anti-PC IgE along with any one or mixture of other isotypes, especially IgG and/or IgA. Accompanying the appearance of these cells in the Peyer's patches following Ascaris infection was the steady rise in IgA committed cells over a 12 week period. The potential to express IgE seems to be a normal feature of the development of secondary or memory cells. The coexpression of IgE randomly with all other isotypes supports a linear rather than a branched pathway of B cell differentiation. Ascaris or PC-determinants given to F1 mice were not unique in their ability to prime cells with the potential for IgE expression. Stimulation of BALB/c mice with two low doses of N-acetyl-glucosamine-conjugated hemocyanin (GlcNAc-Hy) primed cells in vivo generated a high proportion (63%) of clones in vitro that expressed IgE and most of these exclusively coexpressed IgA (16/26) suggesting a progressive restriction in isotype potential. Cells which gave rise to IgE producing clones specific for the priming hapten did not support the expression of IgE by clones of other specificities costimulated in vitro (anti-inulin, anti-beta-galactosyl). Thus the potential to express IgE seems to be both an inherent property of the B cells and under hapten-specific or hapten-linked regulation.
Mol Immunol 1983 Sep
PMID:Interrelationship of primed B cells with the potential for IgE and/or IgA expression. 660 13

To explore mechanisms of gut-mucosal IgA immune response, we have established Con A-induced cloned T cell lines originating from PP and spleen. These cloned cells expressed Thy-1.2+, Lyt-1+2-, Ia (I-A and I-E) and H-2 (K/D) surface antigens. Cloned T cells derived from PP were found to suppress LPS-induced IgM and IgG synthesis and secretion of co-cultured PP B cells; in addition, whereas the PP cloned T cells did not bring about IgA production, they did cause the appearance of large numbers of cells expressing sIgA. In contrast, cloned T cells derived from spleen had little or no effect on LPS-induced IgM synthesis and secretion by PP B cells; in addition, whereas they did suppress IgG production, they neither brought about IgA production nor the appearance of cells expressing sIgA. These studies provide evidence for the existence of a new type of T cell in PP, a switch T cell, which is able to induce B cells to undergo class-specific switches from IgM to IgA; the PP switch T cells appear to govern the pathway of DNA recombination (or RNA splicing) rather than cellular events resulting in terminal differentiation. Thus, these switch T cells are probably responsible for the fact that PP are a major source of mucosal IgA B cells. In additional studies, we show that post-switch IgA B cells, i.e. cells precultured with PP cloned T cells, have the capacity to undergo terminal differentiation into IgA producing plasma cells. provided they are exposed to helper T cells (uncloned) and an appropriate mitogenic stimulus (staphylococcal protein A). We can conclude, therefore, that the development of PP B cells into IgA-producing plasma cells in gut-associated lymphoid tissues (GALT) appears to require at least two steps: one which involves heavy chain switching to IgA and which is governed by IgA class-specific switch T cells in PP, and one which involves differentiation of post-switch B cells and which is governed by helper T cells in lymphoid tissues outside of PP (such as MLN and spleen).
Mol Immunol 1983 Sep
PMID:T cell regulation of IgA immunoglobulin production in gut-associated lymphoid tissues. 660 14

Radioimmunochemical studies on the comparison of the immunological cross-reactivity between the 7-S Igs of birds, reptiles and amphibians (IgY-like Igs) and the IgA of mammals (man and pig) using 125I-chicken IgY and anti-chicken IgY(Fc) or anti-chicken IgY(H) antibodies from rabbits and carp for the detection led to the conclusion that there are close antigenic relationships between them. Therefore, the IgY-like Igs seem to be the precursors for the IgA class of mammals. From that, we give a phylogenetic tree of Igs in accordance with the evolutionary development of vertebrates.
Mol Immunol 1984 Aug
PMID:Evolution of low molecular weight immunoglobulins--IV. IgY-like immunoglobulins of birds, reptiles and amphibians, precursors of mammalian IgA. 661 90


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