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Abnormal Bone Marrow B-Cell Differentiation in Pre-B Lymphoma-prone SL/Kh Mice¹

Department of Pathology [K. o., Y. Y., M. S. O., S. T, Y. N., H. H.] and Urology [K. O., O. Y], Faculty of Medicine, Kyoto University, Yoshida-Konoe-cho, Sakyo-ku, Kyoto 606, and the Laboratory of Experimental Pathology, Aichi Cancer Center Research Institute, Chikusa-ku, Nagoya 464 [H. I.], Japan

² To whom requests for reprints should be addressed.

SL/Kh mice spontaneously develop pre-B lymphomas with surface phenotypes of B220⁺, BP-1⁺, Thy-1^–, and surface immunoglobulin negative. The immunoglobulin heavy chain of lymphoma is clonally rearranged but the light chain gene remains in germline configuration. Studying prelymphoma stage SL/Kh bone marrow (BM), we found unusual multiclonal expansion of BP-1⁺ pre-B cells [34.8 ± 5.8% (mean ± SD)] by 4 weeks of age, whereas there were far fewer of such cells in most other laboratory strains (8 ± 5%). The BP-1⁺ cells did not express surface immunoglobulin, Thy-1.1, or c-kit. Therefore, they seemed to belong to the pre-B II category. Increased numbers of BP-1⁺ cells were seen in F₁ hybrids between SL/Kh and NFS/N; thus it was apparently a dominant heritable property of SL/Kh mice. Emergence of this population was independent of expression of endogenous ecotropic virus, since they were present in BMs of the F₁ hybrid to C4W (Fv-4^r) and were not inhibited by neonatal injection of maternal resistance factor. In the radiation chimeras SL/Kh BALB/c, BP-1⁺ cells appeared abundantly (29.0 ± 3.8%), whereas in the reciprocal chimeras BALB/c SL/Kh, for fewer (5.5 ± 2.3%) appeared. Therefore, expansion of BP-1⁺ cells in prelymphomatous BM is a property of SL/Kh stem cells rather than BM microenvironments.

¹ This work was partly supported by the Grant-in-Aid from the Ministry of Education, Science and Culture, Japan, and by a Grant from Ministry of Health and Welfare, Japan.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

Received 7/27/93. Accepted 11/15/93.

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