B-Lymphoma Models for Tolerance: The Good, the Bad, and the Apoptotic

Murine B-cell lymphomas have become useful models for analyzing the mechanisms of clonal deletion and apoptosis during tolerance, as well as for understanding the regulation of both normal and neoplastic cell growth. In this article, the advantages and disadvantages of these lymphoma models are summarized, and the pathways of signal transduction regulating cell cycle behavior are described. Our studies, and those of several other laboratories, have demonstrated that crosslinking of membrane IgM on a subset of B-cell lymphomas leads to an initial tyrosine phosphorylation event leading to the transcriptional regulation of the c-myc oncogene, subsequent modulation of the phosphorylation of the pRB growth suppressor protein, and cell cycle arrest. This process is followed by apoptosis presumably due to alterations in myc protein turnover. Whether similar events occur during B-cell tolerance in the developing host is discussed.