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Biomedical subjects

E S Vitetta

Publications and source records attributed to E S Vitetta.

At least 253 records · Page 14Linked to original sources
PubMed1981

kappa/lambda Shifts do not occur during maturation of murine B cells.

We have used highly specific affinity-purified antibodies against mouse kappa- and lambda chains in conjunction with both immunofluorescence analysis on the FACS and enzymatic radioiodination of murine splenocytes and bone marrow cells. Our results indicate that the kappa/lambda ratio of cell surface immunoglobulin is constant during the ontogenetic development of B cells, i.e., a shift in the kappa/lambda ratio does not occur during B cell maturation. Our results suggest that the events controlling kappa and lambda expression on murine B cells are decided very early in ontogeny, before significant antigenic selection.

Animals↗
PubMed1981

BCL1, a murine model of prolymphocytic leukemia. I. Effect of splenectomy on growth kinetics and organ distribution.

BCL1 is a transplantable murine B-cell leukemia that closely resembles human prolymphocytic leukemia (PLL). Syngeneic mice injected with BCL1 cells develop massively enlarged spleens followed by leukemia. Splenectomy performed either prior to BCL1 transplantation or prior to the leukemic phase of transplanted BCL1 results in a markedly altered clinical syndrome: the onset of leukemia is delayed by about 2 months; the leukemia is low-grade; and the lymph nodes, which are not prominently involved in leukemic animals with intact spleens, are massively infiltrated in the splenectomized transplant recipient. The immunologic phenotype of the BCL1 cell is not altered by splenectomy and thus does not appear to account for the altered tissue distribution of BCL1 in the splenectomized host. However, the results indicate a striking dependence of BCL1 on microenvironmental influences of the host lymphoid tissues.

Animals↗
PubMed1980

Defective B cell tolerance in adult (NZB X MZW)F1 mice.

Hapten-specific tolerance was induced in vitro by trinitrophenyl-human gamma globulin (TNP32HGG) to a comparable degree in B cells from adult autoimmune (NZB X NZW)F1 (B/W) mice and normal BDF1, CBA/J, and DBA/1J mice. When a lower epitope density tolerogen (TNP7HGG) was used, B/W mice were significantly less sensitive than normal mice to the induction of B cell tolerance. This finding of defective B cell tolerance in adult B/W mice is consistent with previous reports that document other B cell abnormalities that may relate to the expression of autoimmune disease.

Animals↗
PubMed1980

Acquisition of cell surface IgD after in vitro culture of neoplastic B cells from the murine tumor BCL1.

Murine BCL1 tumor cells bear large amounts of surface IgM and trace amounts of surface IgD. In the present studies we have shown that cultivation of these cells, in the absence of lipopolysaccharide, results in the acquisition of IgD by virtually all the cells. These results suggest that BCL1 cells can differentiate in vitro into more mature B cells and offer an attractive model for analyzing the factors controlling appearance of IgD on a monoclonal cell line.

Animals↗
PubMed1980

Selective killing of normal or neoplastic B cells by antibodies coupled to the A chain of ricin.

Highly specific antibodies (affinity-purified or hybridoma) directed against cell surface immunoglobulins on normal or neoplastic murine B lymphocytes were covalently coupled to the A chain of the plant toxin ricin. Such conjugates containing antibodies specific for IgM, for either of the two allotypes of IgD, or for the idiotype of the B cell tumor BCL1 rapidly bound in vitro to cells expressing the corresponding surface antigen and inhibited protein synthesis in such cells. The results demonstrate that A chain-coupled anti-idiotype antibody may be useful as a tumor-specific cytotoxic agent.

Animals↗
PubMed1980

The murine B cell response to TNP-polyacrylamide beads: the relationship between the epitope density of the antigen and the requirements for T cell help and surface IgD.

Spleen cells were cultured with high or low epitope TNP-polyacrylamide beads (TNP-PAB) in order to investigate the effect of epitope density on the requirements for T cell help and surface IgD on responding B cells. The response to low epitope density TNP-PAB was abolished by treatment with anti-Thy-1.2 and complement, whereas approximately 50% of the response to high epitope density TNP-PAB was retained after similar treatment. Thus, an increase in epitope density resulted in a decreased requirement for T cell help. An increase in epitope density was also associated with a decreased requirement for interaction of antigen and surface IgD as determined by "blocking" studies with anti-delta; further, the majority of the T-independent portion of this response was not blocked by anti-delta antibodies. This finding indicate that the T-independent portion of the anti-TNP response does not require interaction of antigen with surface IgD on B cells. These results are discussed in terms of differential cross-linking of IgM and IgD receptors on B cells by multivalent antigens.

Acrylamides↗
PubMed1980

A peptide difference between the mu-chains from cell-associated and secreted IgM of the BCL1 tumor.

The murine B cell tumor, BCL1, bears monomeric IgM lambda on its surface. After stimulation in vitro with LPS, the cells secrete pentameric IgM lambda. Comparison of mu-chains from radiolabeled intracellular, surface, and secreted IgM indicates that mu-chains from the three sites have different apparent m.w. Since the observed differences are analogous to those reported for normal murine lymphoid cells, the BCL1 cells were used for determining the structural basis for the differences in m.w. of mu-chains from the above sites. Comparative peptide analysis was performed on mu-chains from cell associated and secreted IgM. Approximately 25 peptides were identified after digestion with chymotrypsin and trypsin and analysis of peptides by cation exchange chromatography. All peptides co-eluted with the exception of a single extra peptide derived from the Fc portion of the secreted IgM. The same peptide was observed in a similar analysis using mu-chains from IgM secreted by normal splenocytes.

Animals↗
PubMed1980

The effect of anti-immunoglobulin antibodies on the in vitro proliferation and differentiation of normal and neoplastic murineB cells.

In these studies, we have compared the effects of anti-mu and anti-delta antibodies on normal and neoplastic murine B cells. Spleen cells from normal BALB/c mice or from mice carrying the BCL1 tumor were treated with F(ab')2 fragments of affinity purified anti-mu or anti-delta antibodies and the effec of the antibodies on cell proliferation was assessed. F(ab)'2 fragments of both antibodies induced proliferation of normal adult B cells but inhibited (anti-mu) or had no effect (anti-delta) on proliferation of BCL1 cells. In addition, both antibodies further enhanced the LPS-induced proliferative response of cells from adult mice. In contrast, the LPS responses of neonatal cells and BCL1 cells were inhibited by F(ab')2 anti-mu antibodies. These data indicate that interaction of antibody with surface IgD as well as surface IgM can activate adult B cells. In addition, the results provide further evidence that BCL1 cells are neoplastic analogs of immature B cells since the tumor cells, like neonatal cells, are not activated after treatment with anti-Ig antibodies.

Animals↗
PubMed1980

Analysis and detection of B cell neoplasms.

Cells from human B cell lymphomas were analyzed by means of the fluorescence-activated cell sorter (FACS) according to the amount of kappa or lambda immunoglobulins (Ig) on their surface. The crucial requirements for sensitive recognition of small numbers of tumor cells admixed in a normal population are described. Tumor cells were identified as an excess of cells bearing one light chain type ('clonal excess') at discrete levels of fluorescence intensity. Normal patterns of fluorescence staining are compared to those for tissues infiltrated with tumor. For B cell neoplasms with surface Ig of weak intensity, such as chronic lymphocytic leukemia, as few as 1% of the tumor cells admixed with normal cells could be detected; the bright surface fluorescence of cells from lymphoma permitted their recognition when only 0.1% of the tumor cells were present. FACS analysis was carried out on the peripheral blood of a series of patients with B cell lymphoma whose blood was normal by classic cytologic and cytochemical analysis. Nevertheless, circulating tumor cells were recognized in the majority of cases, suggesting that 'subclinical leukemia' is a common finding in B cell lymphomas.

B-Lymphocytes↗
PubMed1980

Structural studies on the murine Ia alloantigens. VII. Further evidence for two-gene control of the E/C alloantigens.

By utilizing comparative tryptic peptide analysis of the E/C alloantigens from additional H-2 recombinant strains, the gene encoding the E/C beta subunit was localized to the I-A or B subregions. By peptide mapping techniques, the E/C alpha- and beta-chains showed little structural homology with the A alloantigen alpha and beta subunits. In addition, comparisons of the E/C beta subunits from F1 strains (b x d) with those from both parental strains revealed that in a heterozygote the beta subunit from either allele (b or d) can associate with the alpha-chain from one allele (d). Thus, the formation of hybrid E/C antigens by cis-trans gene complementation increases the E/C alloantigen repertoire in heterozygotes.

Amino Acid Sequence↗
PubMed1980

Analysis of thymus-leukemia (TL) antigens with monoclonal antibodies.

Lysates of radioiodinated thymocytes have been sequentially immunoprecipitated with monoclonal antibodies specific for thymus-leukemia (TL) antigens. The TL antigenic specificities defined by the monoclonal antibodies appear not to correspond precisely to specificities previously defined with conventional alloantisera. Nonetheless, each of two monoclonal antibodies specific for a single TL determinant was found to deplete lysates of B6.Tlaa thymocytes of all molecules precipitable by an alloantiserum specific for the conventionally defined determinants TL.1,2,3,5, and 6. These results suggest that on B6.Tlaa thymocytes, all the conventional TL antigenic specificities (TL. 1,2,3,5,6) as well as the specificities defined by the monoclonal anti-TL antibodies (TL.m2,m3) are carried by a single molecular species.

Animals↗
PubMed1979

Organization of the immune response genes.

The I region of the major histocompatibility complex contains immune response genes that display considerable polymorphism; that is, there are many alleles at each locus. These genes regulate the immune response to antigen by mediating intercellular communication among lymphoreticular cells. An analysis of the primary structure of the products of two subregions of (I-A, I-E/C) was undertaken in order to understand the genetic organization of the region, the evolution of the genes and, eventually, their function.

Alleles↗
PubMed1979

Structural studies on the murine Ia alloantigens. V. Evidence that the structural gene for the I-E/C beta polypeptide is encoded within the I-A subregion.

The E/C alpha- and beta-subunits of intra-I-region recombinants were analyzed for primary structural variation by comparative tryptic peptide mapping. The E/C alpha-polypeptides from B10.A, B10.A (3R) and B10.A (5R) showed complete coincident elution of peptides; the E/C beta-chains from B10.A and 3R (or 5R) were approximately 40% different. This suggests that the structural gene for the E/C beta-polypeptide is within the I-A subregion.

Amino Acid Sequence↗