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Expression and function of the chemokine, CXCL13, and its receptor, CXCR5, in AIDS-associated non-Hodgkin's lymphoma

AIDS-associated Non-Hodgkin's lymphoma (AIDS-NHL) remains a problem even in the era of effective anti-retroviral therapy. Recent studies have suggested that the chemokine, CXCL13, and its receptor, CXCR5 may play a role in B cell tumors (non-AIDS-associated). Normally, CXCL13 is expressed in secondary lymphoid tissues and directs the homeostatic movement of CXCR5(+) B cells through these areas.

To evaluate the role that CXCL13 and CXCR5 might play in AIDS-NHL, serum of individuals (n = 46) who ultimately developed AIDS-NHL was obtained from the Multicenter AIDS Cohort Study (MACS) at UCLA. The AIDS-NHL serum specimens tested were collected at a mean of 8.9 months prior to NHL diagnosis (SD = 7.9 months). Sera from AIDS (non-lymphoma), healthy HIV-positive, and HIV-negative control subjects were also included in the study. The mean CXCL13 level in the AIDS-NHL group (158 pg/ml, SD = 153) was ~50 percent higher than the AIDS control group (98.4 pg/ml, SD = 70.9, P = 0.02). Furthermore, CXCL13 levels correlated with sCD44 levels in the AIDS-NHL group (R = 0.31, P = 0.04), but not in the AIDS control group (R = 0.07; P = 0.7, data not shown); we previously showed that sCD44 levels are elevated prior to AIDS-NHL development. CXCL13 levels in the AIDS-NHL group were also ~2.5 times greater than levels in the HIV-positive group, and ~7 times greater than levels in the HIV-negative group (P < 0.001 for both comparisons).

Next, tissue arrays were obtained from the AIDS & Cancer Specimen Resource (ACSR) that contained numerous sections of primary AIDS-NHLs, including both the Burkitt and diffuse large cell subtypes. By immunohistochemistry, all primary AIDS-NHLs (24/24) expressed CXCR5, and 22/24 of the AIDS-NHL specimens also showed expression of CXCL13. Cell lines derived from primary AIDS-NHL tumors also showed strong expression of CXCR5, and occasionally, low levels of expression of CXCL13. AIDS-NHL cell lines also demonstrated chemotaxis towards CXCL13.

These results indicate that CXCL13 and CXCR5 may play a role in the biology of AIDS-NHL, possibly by affecting the movement of pre-malignant and/or malignant B cells.

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Correspondence to DP Widney.

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Open Access This article is published under license to BioMed Central Ltd. This is an Open Access article is distributed under the terms of the Creative Commons Attribution 2.0 International License (https://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Keywords

  • Lymphoma
  • Cancer Specimen
  • Serum Specimen
  • Tissue Array
  • Cell Subtype