B lymphocytes are an important cellular component of the adaptive immune system. When normal B-cell development goes awry, B-cell neoplasia can result. B cell neoplasms include multiple myeloma, mantle cell lymphoma and chronic lymphocytic leukemia. Multiple myeloma is a malignant plasma cell disorder and is the second most common hematologic malignancy in the United States, with about 20,000 patients diagnosed annually. Most patients diagnosed with multiple myeloma survive for only 2-3 years. In contrast, patients with mantle cell lymphoma may survive between 5 and 7 years. However, for most multiple myeloma patients, the disease eventually progresses or returns, and over time treatment resistance often develops. Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia. In the U.S. alone, about 15,000 patients will be diagnosed with CLL in 2013, and almost 5,000 deaths from CLL will occur. MDS is diagnosed in more than 15,000 new patients per year, and deletions of chromosome 5 q are the most common cytogenetic abnormality. As with virtually all cancers, prognosis is improved by the early identification of disease and initiation of an appropriate therapeutic regimen. Similarly, it is important to detect treatment resistance to a particular agent early, so that alternate forms of therapy can be provided. IMiDs, such as lenalidomide, pomalidomide and thalidomide may be useful for the treatment of CLL and related disorders. The therapeutic development of such agents would be advanced by the availability of a rodent model capable of responding to these agents, as human cells do. To date, such models have been lacking.