BALB/c mice are highly susceptible (S) to plasmacytoma (PCT) induction protocols while DBA/2 mice are resistant (R). Previously we examined the cellular basis for this phenomenon by transferring BALB/c or DBA/2 bone marrow (BM) to SCID mice and injecting the chimeras with either pristane, or the retrovirus J3V1 containing deregulated myc and raf oncogenes. Using these induction protocols we determined that DBA resistance could not be overcome by the susceptible SCID microenvironment suggesting that R/S, in this system, is dictated by the donor BM. Recent studies of SCID mice reconstituted with peripheral, mature BALB/c lymphocytes either alone, or co-transferred with DBA/2 BM suggest the following: 1.) Mature BALB/c B cells from spleen, lymph node or Peyer's patches are equally susceptible to tumor induction; 2.) DBA/2 cells do not suppress BALB/c PCT development; and 3.) BALB/c lymphocytes can not supply DBA/2 B cells with the extra- cellular signals required for PCT development. Thus, DBA/2 resistance and BALB/c susceptibility to PCT induction are traits inherent to the respective B cells. II. SCID mice have also been used to study normal lymphocyte development and life-span. Previously, we determined that adoptive transfer of Peyer's patch cells to SCID mice resulted in normal reconstitution of all lymphoid tissues except the thymus in which there appeared only single positive CD4 and CD8 mature T cells. We have expanded these studies to determine the duration of this reconstitution and the reconstituting potential of peripheral (PLN) and mesenteric (MLN) lymph node cells. Results indicate that: 1.) PLN cells reconstitute peripheral lymphoid organs, but are less effective at repopulation of the gut mucosal tissues than Peyer's patch cells; 3.) The thymii of PLN and MLN reconstituted SCID mice contain donor CD4 and CD8 single positive mature T cells; and 4.) PP, MLN and PLN repopulation persists for greater than 6 months. These results demonstrate that the lifespan of mature lymphocytes is longer than previously suggested. Moreover, the homing properties of these cells in SCID mice indicate that mucosal and peripheral lymphocytes differ in their ability to modulate homing receptor expression and consequently their pattern of lymphoid tissue reconstitution.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Intramural Research (Z01)
Project #
1Z01CB005553-23
Application #
3796451
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
23
Fiscal Year
1992
Total Cost
Indirect Cost
Name
Division of Cancer Biology and Diagnosis
Department
Type
DUNS #
City
State
Country
United States
Zip Code