Analysis of Ly-1+ B-cell populations and IgH rearrangements in "normal" spleens and in lymphomas of AKR/J and AKR Fv-1b mice.

AKR mice are highly susceptible to development of spontaneous T-cell lymphoma. Thymus removal at the age of 1-3 months greatly reduces T-cell lymphoma. Lymphomas that have the characteristics of T- and/or B-cells occur sporadically in peripheral lymphoid tissues of old thymectomized AKR/J mice. These thymectomized mice were shown to carry dormant potential lymphoma cells. Transplantation of lymphoid cells from 8-12-month-old AKR/J mice, thymectomized at the age of 6 to 8 weeks, into intact or thymectomized young recipients yielded 80-100% Ly-1+ pre-B or B-cell lymphomas. In the AKR-Fv-1b congenic strain the Fv-1n allele of AKR/J mice was substituted with the Fv-1b allele, thereby limiting viral replication and spread of the endogenous N-tropic murine leukemia virus. As a result of this restriction in virus spread, AKR-Fv-1b mice develop a low spontaneous incidence (7%) of T-cell lymphomas and about 28% of Ly-1+ B-cell lymphomas at old age. In spleens of 15-18-month-old thymectomized AKR/J mice and intact AKR-Fv-1b mice, 30-60% of the B-cells were of the Ly-1+ B type. Analysis of the IgH locus in these normal old spleens and Ly-1+ B lymphomas indicated mono- or oligoclonality. One particular IgH rearrangement was identified in many individual old spleens and tumors. A second specific IgH rearrangement was found in some tumors. Possible mechanisms involved in the expansion of Ly-1+ clones and their progression into tumors are discussed.