Herpes simplex virus produces primary and latent infections with periodic recurrency. The prime-boost immunization strategies were studied using a DNA vaccine carrying the full-length glycoprotein D-1 gene and a baculovirus-derived recombinant glycoprotein D, both expressing herpes simplex virus glycoprotein D-1 protein. Immunization with recombinant DNAs encoding antigenic proteins could induce cellular and humoral responses by providing antigen expression in vivo. Higher immune response, however, occurred when the recombinant proteins followed DNA inoculation. While all groups of the immunized mice and positive control group could resist virus challenge, a higher virus neutralizing antibody level was detected in the animals receiving recombinant protein following DNA vaccination.
B-1 (CD5+ B) cells appear early in ontogeny, produce mainly unmutated polyreactive antibodies, and are capable of self-renewal. B-1 cells clonally expand with age and are the malignant cell in chronic lymphocytic leukemia. In this report immunological analysis of B-1 malignancies in NZB mice, a murine model of chronic lymphocytic leukemia, is related to current information on B-1 cells. B-1 clones from NZB mice produce high levels of interleukin-10, detected at the RNA level by semi-quantitative polymerase chain reaction. In addition, the B-1 malignant clones in NZB mice and their hybrids, are negative for B220/6B2 expression, the B-specific antigenic form of CD45 which is a membrane-associated phosphatase involved in lymphocyte activation. Both the autocrine production by B-1 cells of interleukin-10 and altered CD45 expression may be responsible for the clonal expansion of these cells, as well as the accompanying T cell expansion. We report the establishment of an in vitro cytotoxic CD8+ T cell line derived from an NZB with a B-1 malignancy. The effect of B-1 cell-derived interleukin-10 on subsets of T lymphocytes may account for the immunoregulatory properties of B-1 cells. In addition, the NZB malignancies were also characterized for immunoglobulin variable region sequence and antigen specificity. The B-1 malignancies produced immunoglobulin derived from unmutated germline sequences with no N base substitutions. It appears that both the immunoglobulin and interleukin-10 produced by the B-1 malignant cell in NZB mice may have immunoregulatory properties. A study of B-1 malignancies may shed light on the immunoregulatory properties of non-clonally expanded normal B-1 cells.
Human chronic lymphocytic leukemia (CLL) is a malignancy of B-1 cells characterized by the accumulation of mature appearing, long lived, slow growing B-1 cells in peripheral blood. CLL occasionally evolves into an aggressive large cell lymphoma termed Richter's syndrome. NZB mice can be used to model the early stage of CLL because aged NZB mice can spontaneously develop slow growing malignant B-1 cell clones. The malignant NZB B-1 clones fail to grow in culture and are typically carried in vivo as passaged lines. During serial passage, an aggressive lymphoma developed as a result of a continued transformation of the original B-1 clone, similar to the development of Richter's syndrome. An in vitro cell line was established from the aggressive lymphoma, which was stromal dependent and could rapidly metastasize when passaged into recipient animals. Analysis of adhesion molecules did not reveal any consistent characteristics that could account for the metastatic potential of the Richter's-like cells. In addition, the aggressive in vitro line had the identical heavy chain sequence as the slow growing NZB malignant B-1 clones. The in vitro and in vivo aggressive B-1 cells had very high levels of IL-10 message, and underwent more apoptosis in response to anti-IgM than did nonaggressive B-1 clones. Taking these characteristics together, we have composed a comprehensive animal model system for human CLL that includes both the aged NZB mice for the early stage and the recipients of the in vitro B-1 line for the late stage or Richter's syndrome. This model system can be used to study, not only the ontogeny and genetic linkage of CLL, but also the regulatory factors involved in transformation and growth both in vivo and in vitro.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.