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Multi-parameter analysis of SWXJ recombinant inbred strains suggest common cross-strain properties of spontaneous germinal center B cell lymphomagenesis



Multi-parameter analysis of SWXJ recombinant inbred strains suggest common cross-strain properties of spontaneous germinal center B cell lymphomagenesis



FASEB Journal 15(5): A1180, March 8



SJL lymphomas (RCS) occur in apprx90% of 13 month old mice and express novel META-env initiated Mtv29 transcripts encoding a viral superantigen (vSAg) which stimulates Vbeta16+CD4+ T cells needed for their growth. RCS are germinal center (GC) derived and surface PNA+B220+; their development is preceded by the appearance of serum paraproteins (PP). C57L (Mtv29+) lymphomas share these characteristics, but develop later and with lower incidence, probably due to high NK activity of this strain. In this study, 14 SWXJ recombinant inbred strains derived from the lymphoma prone SJL (H25, low NK, Mtv29+,7-) and resistant SWR (H29, high NK, Mtv29-,7+) strains were characterized. SWXJ-7 (H29, Low NK, Mtv29+,7-) had a lymphoma incidence of apprx30% and 22% IgA and 15% IgG PP by 13 months. SWXJ-1 (H25, NK?, Mtv29-,7+) had a 57% incidence of lymphoma accompanied by 29% IgA and 29% IgG PP at 13 months. Several other SWXJ strains which had a lymphoma incidence of <10% by this age (5 with a high NK phenotype) also had PP in their sera, consistent with our previous observations in SJL mice where lymphoma cells did not produce the PPs. All SWXJ-1 and some SWXJ-7 lymphomas were lymphoblastoid PNA+B220+ cells, that resembled RCS, and developed in lymph nodes, spleen and Peyer's patches. gamma-irradiated B220+ lymphoma cells induced vigorous proliferation of SWRxSJL T cells. A META-env initiated Mtv7-encoded vSAg was expressed in SWXJ-1 lymphomas which, like vSAg29, stimulated Vbeta16+CD4+ T cell hybrids. These data suggest that development of GC-derived lymphomas in mice is more common than originally thought, and consistently involves MMTV encoded vSAg expression.

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Accession: 035349391

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