Carcinogenesis, Vol. 20, No. 4, 529-538,
April 1999
© 1999 Oxford University Press
Murine plasmacytomas, carrier of the t(12;15) chromosomal translocation, develop from immature/mature B cells not from differentiated plasma cells
Department of Molecular Immunology, Cancer Research Institute and
1 Faculty of Medicine, Institute for Experimental Animals, Kanazawa University, 13-1, Takara-machi, Kanazawa 920-0934, Japan and
2 Microbiology and Tumor Biology Center, Karolinska Institute, S-171 77 Stockholm, Sweden
Dysregulation of the c-myc gene by chromosomal translocation in >95% of murine plasmacytomas (MPCs) is an obligatory requirement for the transformation of B lymphocytes into MPCs. However, it is still unknown whether sIg+ B cells or differentiated plasma cells are the legitimate precursor cells from which MPCs develop. To address this question, C.B-17 scid/scid (SCID) mice were reconstituted with splenic surface Ig-positive (sIg+) B lineage cells originating from BALB/cRb6.15 (B/cRb6.15) or human IL-6 transgene-congenic BALB/cRb8.12 mice (B/cRb8.12 IL-6-Tg). Six of 80 SCID mice reconstituted with B/cRb6.15 sIg+ B cells developed MPCs after pristane (2,6,10,14-tetramethylpentadecane) treatment followed by Abelson murine leukemia virus (A-MuLV) infection (incidence 7.5%) and four of 40 after pristane treatment alone (incidence 10%). Similarly, in 20 SCID mice reconstituted with B/cRb8.12 IL-6-Tg splenic sIg+ B cells the MPC incidence was 10%. Karyotype analysis revealed that all the translocations were of typical t(12;15) type and all tumors carried the Rb6.15 or Rb8.12 marker chromosome, indicating their donor cell origin. In contrast, none of the 48 SCID mice reconstituted with plasma cells obtained from the lymph nodes of B/cRb8.12 IL-6-Tg mice developed MPCs when treated either with pristane plus A-MuLV (20 mice) or with pristane alone (28 mice), although the transferred plasma cells were still functional in the recipient SCID mice 6 months after transfer. The findings indicate that the malignant transformation triggered by Ig/myc juxtaposition occurs more in immature (sIgM+) and/or mature (sIgM+/sIgD+, sIgG+ and sIgA+) B cells than in differentiated G0 or cycling plasma cells. We inferred that immature and/or mature B cells and not differentiated plasma cells are most likely the principal source of precursor cells from which the typical t(12;15) MPCs develop.
Abbreviations: A-MuLV, Abelson murine leukemia virus; B/cRb6.15, BALB/cRb6.15; B/cRb8.12, BALB/cRb8.12; B/cRb8.12 IL-6-Tg, BALB/cRb8.12 IL-6 transgenic; FCS, fetal calf serum; LN, lymph node; LTR, long terminal repeat; MPC, murine plasmacytoma; OG, oil granuloma; PBS, phosphate-buffered saline; pre-B, precursor B cell; pro-B, B cell progenitor; sIg+, cell surface Ig-positive; sIg–, cell surface Ig-negative; Rb, Robertsonian; SSLP, simple sequence repeat length polymorphism.
3 To whom correspondence should be addressed Email: shinohno{at}kenroku.kanazawa-u.ac.jp