Molecular Features of Lymphoproliferation in Mixed Cryoglobulinemia

The identification and characterization of the B-cell population responsible for the production of IgM with rheumatoid factor activity are important in order to understand the pathogenetic mechanism leading to type II cryoglobulinemia and overt B-cell lymphoma development. Based on recent progress in the molecular and cell biology of self-reactive B cells in HCV-associated mixed cryoglobulinemia, it has become clear that a substantial proportion of clonal B cells consist of unswitched CD27+ memory B cells with the inherent property of IgM receptor expression. In this chapter, we report the latest information on the molecular implication of IgM receptors in the context of HCV infection, transinfection, and autoimmune B-cell survival. A relationship between the Blys receptor, BR3, and IgM+VH1-69+ B cells, including the regulation of B-cell receptor signaling and cell homeostasis, has been suggested; however, many questions remain to be answered.