Murine plasmacytomas, carrier of the t(12;15) chromosomal translocation, develop from immature/mature B cells not from differentiated plasma cells

Dysregulation of the c-myc gene by chromosomal translocation in >95% of mur ine plasmacytomas (MPCs) is an obligatory requirement for the transformatio n of B lymphocytes into MPCs, However, it is still unknown whether sIg(+) B cells or differentiated plasma cells are the legitimate precursor cells fr om which MPCs develop. To address this question, C.B-17 scidlscid (SCID) mi ce were reconstituted with splenic surface Ig-positive (sIg+) B lineage cel ls originating from BALB/cRb6.15 (B/cRb6.15) or human IL-6 transgene-congen ic 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-tetra methylpentadecane) treatment followed by Abelson murine leukemia virus (A-M uLV) infection (incidence 7.5%) and four of 40 after pristane treatment alo ne (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 analys is revealed that all the translocations were of typical t(12;15) type and a ll 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 devel oped MPCs when treated either with pristane plus A-MuLV (20 mice) or with p ristane alone (28 mice), although the transferred plasma cells were still f unctional in the recipient SCID mice 6 months after transfer. The findings indicate that the malignant transformation triggered by Ig/myc juxtapositio n occurs more in immature (sIgM(+)) and/or mature (sIgM(+)/ sIgD(+), sIgG() and sIgA(+)) B cells than in differentiated Go or cycling plasma cells, W e inferred that immature and/or mature B cells and not differentiated plasm a cells are most likely the principal source of precursor cells from which the typical t(12;15) MPCs develop.