R01-CA57152 to OM-M, by R01-CA107023 to MLP, by an National Cancer Insitute-funded pilot/seed grant provided to OM-M through the University of California Los Angeles (UCLA) Center for AIDS Research (funded by This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.įunding: This work was supported, in part, by National Institutes of Health (NIH) grants R01-CA-168482 and Received: JAccepted: JPublished: August 2, 2013Ĭopyright: © 2013 Widney et al. PLoS ONE 8(8):Įditor: Ann M Moormann, University of Massachusetts Medical School, United States of America (2013) Levels of Murine, but Not Human, CXCL13 Are Greatly Elevated in NOD-SCID Mice Bearing the AIDS-Associated Burkitt Lymphoma Cell Line, 2F7. This mouse model may be useful for future studies on the interactions of the innate immune system and AIDS-BL tumor cells, as well as for the assessment of potential tumor biomarkers for this disease.Ĭitation: Widney DP, Olafsen T, Wu AM, Kitchen CMR, Said JW, Smith JB, et al. These results also identify CXCL13 as a potential biomarker for this disease, which is consistent with previous studies showing that serum levels of CXCL13 were elevated in human subjects who developed AIDS-lymphoma. The marked elevations in tumor cell CXCR5 expression and in murine CXCL13 levels seen in the model may potentially identify an important link between tumor-interacting histiocytes and tumor cells in AIDS-BL. Blocking CXCR5 on 2F7 cells with neutralizing antibodies prior to injection into the mice substantially delayed tumor formation. As shown by immunohistochemistry, murine CXCL13 was associated with macrophage-like tumor-infiltrating cells that appeared to be histiocytes. CXCL13 is the ligand for CXCR5, and serum and ascites levels of murine, but not human, CXCL13 showed a striking elevation in tumor-bearing mice, with levels as high as 200,000 pg/ml in ascites, as measured by ELISA. Expression of the chemokine receptor, CXCR5, was greatly elevated in vivo on BL tumor cells in this model, as shown by flow cytometry. Mice developed tumors in the peritoneal cavity, with metastases to the spleen, thymus, and mesenteric lymph nodes. In these studies, a novel mouse/human xenograft model of AIDS-associated Burkitt lymphoma (AIDS-BL) was created by injecting cells of the human AIDS-BL cell line, 2F7, intraperitoneally into NOD-SCID mice. In addition, they can be used to study the function of nonlymphoid cell types in the absence of lymphocytes.Currently, few rodent models of AIDS-associated non-Hodgkin’s lymphoma (AIDS-NHL) exist. Thus, scid mice are of interest for studies of both normal and abnormal lymphocyte development and function. They also support the growth of allogeneic and xenogeneic tumors. Scid mice readily support normal lymphocyte differentiation and can be reconstituted with normal lymphocytes from other mice and even partially reconstituted with human lymphocytes.

By 10-14 months of age, virtually all scid mice are leaky. The arrest in lymphocyte development is not absolute some young adult scid mice are 'leaky' and generate a few clones of functional B and T cells. The mutation appears to impair the recombination of antigen receptor genes and thereby causes an arrest in the early development of B and T lineage-committed cells other hematopoietic cell types appear to develop and function normally.

Mice homozygous for the scid mutation (scid mice) are severely deficient in functional B and T lymphocytes.

What is nod scid