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Biomedical subjects

D L Mann

Publications and source records attributed to D L Mann.

At least 235 records · Page 13Linked to original sources

B-lymphocyte alloantigens associated with systemic lupus erythematosus.

We examined B-lymphocyte alloantigens in 41 patients with systemic lupus erythematosus and 184 controls, using a panel of 47 pregnancy serums, and compared reaction frequencies of individual serums. One serum, la-715, reacted with B lymphocytes from 75.6 per cent of patients and 14.1 per cent of controls (Pc less than 0.005, relative risk 18.8). Twenty-eight of the patients were also typed with a panel of HLA-D-related serums from the Seventh International Histocompatibility Workshop, HLA-DRw types assigned, and compared to 490 Workshop controls. Both HLA-DRw2 (57.1 per cent vs. 26.4 per cent, Pc less than 0.004) and HLA-DRw3 (46.4 per cent vs. 22.2 per cent, Pc less than 0.03) were increased in systemic lupus erythematosus. This study demonstrates that select B-lymphocyte alloantigens, which are controlled by genes in the major histocompatibility complex, are present in increased frequency in systemic lupus erythematosus.

Adolescent↗

B lymphocyte antigens in sicca syndrome.

All individuals tested in this study with sicca syndrome, a human autoimmune disease, bear two immunologically distinct and genetically unrelated B lymphocyte antigens that appear similar to the immune response associated (Ia) antigens of the mouse. The genes coding for these two antigens are present in only 37 and 24 percent of normal controls. In animal models Ia antigen genes are closely linked to immune response genes. Our findings suggest that two such genes may be required for the development of sicca syndrome.

Adolescent↗

Genetic control of B-cell alloantigens: evidence for gene(s) linked to the HLA-A locus.

Families with known HLA recombinant individuals were typed for B-lymphocyte alloantigens. The B-cell alloantigens were found to be inherited with the intact HLA haplotypes. However, the results of the typing of the recombinant individuals indicated that specific antigens are associated with the HLA-A locus and/or with the HLA-B locus. These studies indicate that more than one gene initiates the expression of these antigens and that some of these genes may map between the HLA-A and HLA-B loci.

B-Lymphocytes↗

Immunogenetic determinants of familial acute lymphocytic leukemia.

Acute lymphocytic leukemia developed almost simultaneously in two adolescent brothers, and another brother and both parents had rheumatoid arthritis. Laboratory studies uncovered no evidence for an underlying immunodeficiency state in the family. Immunogenetic evaluation showed the leukemic siblings to be HLA- and mixed-leukocyte-culture identical and homozygous for a recessively inherited locus dictating the presence of antigens on the surface of B-cells. This Ia antigen, as detected by sera from mothers of leukemic children, appeared to be mapped within the major histocompatibility region and may be a human analogue to murine immune-response antigens associated with susceptibility to leukemia.

Adolescent↗

Genetic basis of gluten-sentitive enteropathy.

Families of patients with gluten-sensitive enteropathy (GSE) were typed for HLA-A and -B antigens as well as for HLA-DW3 antigen(s) using appropriate typing alloantisera. In addition, patients and families were typed for GSE-associated B cell antigens using alloantisera obtained from mothers and wives of patients. The data obtained suggest that disease occurs within families when two conditions were fulfilled: (1) the family member is homozygous for the GSE-associated B cell antigens and (2) the family member also bears the HLA-DW3 antigen(s) or an antigen usually associated with DW3. In addition, with the family studies it was possible to show that the gene(s) controlling the DW3 antigen(s) and those controlling the GSE-associated B cell antigens are separate nonlinked genetic loci, a fact which leads to the conclusion that GSE has a genetic basis in at least two genes. It is speculated that the genes responsible for GSE code for surface proteins which are physically associated on lymphoid cell membranes and which form receptors important to the initiation of disease.

B-Lymphocytes↗

Purification of HLA-linked B lymphocyte alloantigens in immunologically active form by preparative sodium dodecyl sulfate-gel electrophoresis and studies on their subunit association.

The HLA-linked B cell alloantigen (p29,34) is composed of two subunits of 29,000 (p29) and 34,000 (p34) molecular weight. The partially purified HLA-linked B cell alloantigen was purified by a final step of preparative sodium dodecyl sulfate-gel electrophoresis. An antiserum was prepared against p29,34 which specifically lysed B lymphocytes. In sodium dodecyl sulfate at 21 degrees, p29 and p34 remained noncovalently associated and retained immunologic activity; subunit dissociation at higher temperatures correlated with loss of immunologic activity. Although the pI values of p29 and p34 are 6.1 and 5.2, respectively, the subunits co-electrofocus under nondenaturing conditions. In addition, cross-linking studies showed the B cell antigen has a (p29)1(p34)1 subunit structure.

Antigen-Antibody Reactions↗

Detergent solubilization, purification, and separation of specificities of HLA antigens from a cultured human lymphoblastoid line, RPMI 4265.

HLA antigens have been purified to homogeneity after detergent solubilization from RPMI 4265, a human lymphoblastoid line. The inhibition of cytotoxicity assay for HLA antigen was modified, using preincubation with bovine serum albumin of antigen samples containing detergent to prevent lysis of target cells by detergent. Solubilization was tested with many types of detergents. A polyethyleneglycol oleyl ether nonionic detergent mixture, Brij 99:Brij 97 (2:1) was selected for solubilization, since it selectively solubilized HLA antigens, had a low absorbance at 280 nm and was uncharded. HLA antigens were then purified by Lens culinaris lectin affinity chromatography and Bio-Gel A-5m filtration. The antigen specifity HLA-A2 was separated from specificities HLA-B7,12 by isoelectric focusing. Purified HLA antigens contained a subunit of Mr=44,000 with NH2-terminal glycine, and a subunit of Mr=12,000, beta2-microglobulin, with NH2-terminal isoleucine.

Amino Acids↗

Structure of HL-A A and B antigens isolated from cultured human lymphocytes.

From these data, a model was prepared which summarizes schematically our present knowledge of the structure and orientation of the HL-A antigenic molecule in the lymphocyte membrane (Fig. 3). It seems likely that the heavy chain spans the membrane, with the hydrophobic region inserted in the membrane and the hydrophilic C-terminus inside the cell. This C-terminal region bears one (possible two) SH residue which has the potential for forming interchain disulfides. Whether or not these are actually formed physiologically remains an interesting question. There is the attractive possibility that whatever the physiological functions of HL-A antigens are, structurally these molecules provide the potential for signaling from outside the cell to inside the cell because they span the membrane. It is even conceivable that this function might be expressed via the opening and closing of disulfide bridges.

Amino Acid Sequence↗

Frozen-thawed mononuclear cells as a source of B lymphocytes for antibody screening.

B lymphocytes were isolated from fresh blood and frozen-thawed lymphocyte preparations from the same donors. A panel of 55 human antisera, previously found to react with human peripheral blood B lymphocytes in cytotoxicity assays, was screened against these B-cell preparations. There was essentially no difference in the reactions of B-cell antisera with fresh B lymphocytes when compared with frozen-thawed cells. The percentage recovery of B cells from the fresh and frozen preparations was not significantly different.

B-Lymphocytes↗

Distribution of alloantigens on human Fc receptor-bearing lymphocytes: the presence of B cell alloantigens on sIg-positive but not sIg-negative lymphocytes.

Human peripheral blood lymphocyte subpopulations were analyzed for the presence of B cell alloantigens with a microcytotoxicity assay. B cell alloantigens were found exclusively on sIg-positive lymphocytes and were not present on sIg-negative, Fc receptor-bearing lymphocytes or sIg-negative, Fc receptor-negative T lymphocytes.

B-Lymphocytes↗

A human alloantiserum precipitates Ia-like molecules from chronic lymphocytic leukemia cells.

Alloantigens specific for human B lymphocytes can be identified with selected antisera. These antigens have similarities to murine Ia antigens in that they are found on human B lymphocytes and are controlled by genes linked to genes controlling HLA. Chronic lymphocytic leukemia cells bearing B cell antigens were labeled with 3H leucine and the membrane components reacting with the B cell antisera isolated by immunoprecipitation. These membrane components had m.w. of 33,000 and 24,000 daltons similar to the murine Ia antigens. The results complete the homology of murine Ia and human B cell alloantigens.

Animals↗

Isolation and immunologic characterization of a human. B-lymphocyte-specific, cell surface antigen.

In addition to HL-A antigens, another cell surface protein complex has been obtained from membranes of the human B-lymphoblast cell line IM-1. This complex which was solubilized with papain, consisted of polypeptides of 23,000 and 30,000 daltons (p23, 30). Rabbit antisera to this material precipitated from [35S]methionine-labeled detergent-solubilized cells, three proteins of 39,000, 34,000, and 29,000 daltons. These antisera were specifically cytotoxic for B lymphocytes of peripheral blood, for B-lymphoblast cell lines, and for EAC rosette receptor-positive surface Ig-negative (Null) lymphocytes. The p23,30 complex was not present on T lymphocytes, EAC rosette receptor-negative Null lymphocytes, or platelets. In addition, the p23,30 complex from several cell lines inhibited alloantisera from multiparous Amish women which had been shown to recognize non-HL-A, B-lymphocyte antigens. Some other properties of the anti-p23,30 sera antisera were described.

Antigen-Antibody Reactions↗

Specific B-cell antigens associated with gluten-sensitive enteropathy and dermatitis herpetiformis.

Gluten-sensitive enteropathy (G.S.E.) and dermatitis herpetiformis (D.H.) are associated with an increased frequency of the histocompatability antigen HLA-B8. These diseases were found to be even more strongly associated with a specific B-lymphocyte surface antigen recognised by maternal antisera. Two antisera (B-1 and W-1) reacted with B lymphocytes form G.S.E. and D.H. patients. Antiserum B-1 reacted with cells from thirteen of sixteen G.S.E. patients and from fifteen of nineteen D.H. patients, while antiserum W-1 reacted with cells from fifteen of sixteen G.S.E. patients and from fifteen of fifteen D.H. patients. None of the sera tested reacted with B lymphocytes from thirty-seven normal individuals, whether or not they were HL8-B8 positive. The identification of this specific antigen provides further insight into the pathogenesis of G.S.E. and D.H. and might form the basic of a diagnostic test for these diseases.

Adolescent↗