Influence of IgH V-region genes on the growth kinetics of a murine B cell leukemia (BCL₁)

The growth kinetics of an IgM-bearing B cell leukemia of BALB/c (Ig-I^a) origin, designated BCL₁, has been investigated in 2 allotype immunoglobulin (Ig) heavy (H) chain congenic strains, C.B-20 (Ig-1^b) and C.AL-20 (Ig-1(d)), and an (H) chain recombinant strain, BAB-14 (Ig-1^a/1^b), that carries Ig-1^a genes in the variable (V)-region and Ig-1^b genes in the constant (C)-region. When large numbers (10⁶ to 10⁷) of BCL₁ cells were injected into these mice, leukemia, as measured by the appearance of leukemic cells in peripheral blood with subsequent mortality, did not occur in C.B-20, was delayed in C.AL-20, and progressed at the same rate in BAB-14 relative to BALB/c control mice. These results indicate that an immune response directed against an antigen encoded for by an H chain V region gene (idiotype or variable-region allotype) or linked gene (minor histocompatibility antigen) prevents the growth of the BCL₁ leukemia in the C.B-20 mice. Tumor resistance appears to be due to T cell activity adoptive transfer of such cells from C.B.-20 tumor rejectors protected sublethally irradiated recipients from subsequent tumor challenge. Although H-2 restricted, anti-BCL₁ cytotoxic cells were detected in C.B-20 mice challenged in vivo and restimulated in vitro with BCL₁ cells, evidence is discussed that suggests that the resistance observed is not due to these effector cells. The resistance of allotype congenic mice to BCL₁ was not absolute; a small inoculum (10²) was as lethal in C.B-20 and C.AL-20 as BALB/c mice. Thus, Ig-encoded cell surface antigens, although immunogenic, in no way ensure ultimate host survival.