the b cell antigen receptor and overexpression of myc can cooperate in the genesis of b cell lymphomasmyc的b细胞抗原受体和超表达可以合作在b细胞淋巴瘤的起源.pdfVIP

PLoS BIOLOGY The B Cell Antigen Receptor and Overexpression of MYC Can Cooperate in the Genesis of B Cell Lymphomas Yosef Refaeli1,2,3¤a*, Ryan M. Young3¤a, Brian C. Turner3¤a, Jennifer Duda1,2, Kenneth A. Field1,2¤b, J. Michael Bishop1,2 1 The George W. Hooper Foundation, University of California, San Francisco, San Francisco, California, United States of America, 2 Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, California, United States of America, 3 Department of Pediatrics, Program in Cell Biology, National Jewish Medical and Research Center, Denver, Colorado, United States of America A variety of circumstantial evidence from humans has implicated the B cell antigen receptor (BCR) in the genesis of B cell lymphomas. We generated mouse models designed to test this possibility directly, and we found that both the constitutive and antigen-stimulated state of a clonal BCR affected the rate and outcome of lymphomagenesis initiated by the proto-oncogene MYC. The tumors that arose in the presence of constitutive BCR differed from those initiated by MYC alone and resembled chronic B cell lymphocytic leukemia/lymphoma (B-CLL), whereas those that arose in response to antigen stimulation resembled large B-cell lymphomas, particularly Burkitt lymphoma (BL). We linked the genesis of the BL-like tumors to antigen stimulus in three ways. First, in reconstruction experiments, stimulation of B cells by an autoantigen in the presence of overexpressed MYC gave rise to BL-like tumors that were, in turn, dependent on both MYC and the antigen for survival and proliferation. Second, genetic disruption of the pathway that mediates signaling from the BCR promptly killed cells of the BL-like tumors as well as the t