Do superantigens play a role in lymphoproliferation?

The T cell superantigens are infectious agents that interact with the T cell receptor and the MHC molecules outside their normal antigen-specific sites, with products of conserved sequences of the variable region chains. This non-specific interaction results in the massive stimulation of T cells (up to 20% of the total) as opposed to conventional antigenic stimulation, which is specific and limited to about 10,000 cells. B cell superantigens have recently been described, stimulating a restricted subset of B cells, those expressing the VH3 subgroup in their rearranged immunoglobulin genes. A number of murine malignancies have been shown to be due to T cell superantigens acting either on T cells or on B cells: the RCS B cell lymphomas in SJL mice, the radiation leukemia virus-induced T cell thymic lymphomas in C57BL/Ka mice and B cell lymphomas in the murine AIDS. We propose that some human B cell malignancies can be due to a similar type of interaction. B cell lymphomas in AIDS patients were recently suggested to be due to the HIV gp120 envelope glycoprotein, a newly recognized superantigen. It can be speculated that the low grade B cell gastric lymphomas of mucosa-associated lymphoid tissue (MALT) are the result of exposure to the H. pylori pathogen. EBV-related lymphocytic proliferation has also been shown to be related with a restricted repertoire and may constitute another example of superantigen driven proliferation. A classification of the various superantigen-driven lymphoproliferative states is proposed.