IL-21–Driven Neoplasms in SJL Mice Mimic Some Key Features of Human Angioimmunoblastic T-Cell Lymphoma
The American Journal of Pathology(2015)
摘要
SJL/J mice exhibit a high incidence of mature B-cell lymphomas that require CD4(+) T cells for their development. We found that their spleens and lymph nodes contained increased numbers of germinal centers and T follicular helper (T-FH) cells. Microarray analyses revealed high levels of transcripts encoding IL-21 associated with high levels of serum IL-21. We developed IL-21 receptor (IL21R)-deficient Swiss Jim Lambart (SJL) mice to determine the role of IL-21 in disease. These mice had reduced numbers of T-FH cells, lower serum Levels of IL-21, and few germinal center B cells, and they did not develop B-cell tumors, suggesting IL-21-dependent B-cell lymphomagenesis. We also noted a series of features common to SJL disease and human angioimmunoblastic T-cell lymphoma (AITL), a malignancy of T-FH cells. Gene expression analyses of AITL showed that essentially all cases expressed elevated Levels of transcripts for IL21, IL21R, and a series of genes associated with T-FH cell development and function. These results identify a mouse model with features of AITL and suggest that patients with the disease might benefit from therapeutic interventions that interrupt IL-21 signaling.
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