November-December 2012, Volume 9, Issue 6
B10 Cells and Immune Suppression in CLL
Published on: November 01, 2012
Dr. Byrd indicated no relevant conflicts of interest.
DiLillo DJ, Weinberg JB, Yoshizaki A, et al. Chronic lymphocytic leukemia
and regulatory B cells share IL-10 competence and immunosuppressive function. Leukemia. 2012. Epub ahead of print.
Our immune system is remarkable in its complexity, existing as a delicate balance between self-protection and self-destruction. This balance is maintained by a counterweight system consisting of regulatory elements (subsets of B, T, and NK cells) that either enhance or dampen the immune response. New contributors to this high-wire balancing act continue to be identified and characterized. Among the recently identified regulatory cells are B10 B-lymphocytes that have the capacity to generate a robust interleukin-10 response thereby functioning as negative regulators of autoimmunity, inflammation, and the innate immune response. Flow cytometric analysis of B10 lymphocytes shows that their cell-surface immunophenotype is similar to that of chronic lymphocytic leukemia (CLL) cells. In the current study, from the laboratory of Thomas Tedder at Duke University, the authors hypothesized that aberrant IL-10 production contributes to the immunodeficient state that characterizes CLL. To investigate their hypothesis, the capacity of CLL cells to secrete IL-10 upon stimulation was analyzed. CLL cells from 90 percent of the study patients (n=93) were IL-10 competent, and the serum concentration of IL-10 was found to be significantly higher in patients with CLL compared with the control population. Moreover, patients with mutated immunoglobulin heavy-chain status were found to have the greatest frequency of IL-10 release, and IL-10 release correlated positively with CLL cell expression of the TCL1 oncoprotein. Taking advantage of this latter observation, the authors investigated the characteristics of B10 lymphocytes and malignant B cells in the TCL1 transgenic model of CLL. DiLillo and colleagues reported that IL-10 competent B cells with the B10 immunophenotype expanded prior to the development of overt CLL in TCL transgenic mice. Treatment of the TCL1 transgenics with low-dose polysaccharide (to simulate a bacterial infection) induced IL-10 expression in CLL cells and was accompanied by high serum concentrations of IL-10. Together, these observations suggest that B10 lymphocytes and their closely related malignant counterparts contribute to the immune deficiency of CLL.
The importance of the current paper is that it extends the initial studies of this group and others that identified B10 lymphocytes by showing phenotypic and functional similarities between this subset of regulatory B cells and CLL cells in both humans and TCL1 transgenic mice (a well characterized murine model of CLL). Together, these results suggest a role for IL-10 in both the pathogenesis and the immune deficiency of CLL. The combination of the wide application of immune-based therapy, such as monoclonal antibodies, that target normal, immunnocompetent cells as well as malignant cells, and the morbidity that comes from infections as a consequent of the immunodeficient state associated with CLL, makes precisely defining the individual degree of immune suppression clinically important. Accordingly, stratification of patients based on IL-10 production could be explored. Targeting IL-10 directly or developing strategies to reduce cellular production of IL-10 might ameliorate the immune deficiency of CLL. Longitudinal studies of the characteristics of B10 lymphocytes in individuals with precursor CLL (monoclonal B-cell lymphocytosis) might provide insights into the mechanisms underlying clonal expansion that leads to development of overt CLL.
back to top