Journal article
Molecular characterization of anti-idiotype antibody-resistant variants of a murine B cell lymphoma
The Journal of immunology (1950), Vol.145(2), pp.768-777
1990
DOI: 10.4049/jimmunol.145.2.768
PMID: 2114449
Abstract
We have previously identified Id- tumor vaiants that emerge after anti-Id mAb therapy of the murine B cell lymphoma 38C13. This report characterizes the molecular basis for these variants. By using a modification of the polymerase chain reaction (PCR), mu and kappa Ig loci were sequenced from nine Id- variants derived directly by anti-Id immunoselection in vivo. Ig kappa loci sequence analysis was also performed from 10 additional variants amplified directly from tumor cells in vitro without immunoselection. We demonstrate that the molecular mechanism underlying tumor cell escape in this model is the spontaneous emergence of variants that have undergone kappa L chain gene "re-rearrangement" before positive selection by the anti-Id antibody. A second round of re-rearrangement was also demonstrated to occur within primary tumor variants. Re-rearrangement of the 38C13 tumor cell Ig kappa locus is strongly biased toward use of variable kappa genes within the conserved V kappa-Ox1 gene family, although their use is not exclusive. With the use of RNA PCR re-rearrangement was documented to occur in vitro at a frequency of approximately 1.0 x 10(-5)/cell. These findings may have important implications for the application of anti-Id antibodies as a therapeutic approach for human lymphomas and for understanding of the Ig gene rearrangement process.
Details
- Title: Subtitle
- Molecular characterization of anti-idiotype antibody-resistant variants of a murine B cell lymphoma
- Creators
- Mark S Roth - University of MichiganGeorge J Weiner - Univ. Michigan, Howard Hughes medical inst., dep. medicine, Ann Arbor MI 48109, United StatesElizabeth A Allen - Univ. Michigan, Howard Hughes medical inst., dep. medicine, Ann Arbor MI 48109, United StatesValeri H Terry - Univ. Michigan, Howard Hughes medical inst., dep. medicine, Ann Arbor MI 48109, United StatesCatherine E Harnden - Univ. Michigan, Howard Hughes medical inst., dep. medicine, Ann Arbor MI 48109, United StatesMichael Boehnke - Univ. Michigan, Howard Hughes medical inst., dep. medicine, Ann Arbor MI 48109, United StatesMark S Kaminski - Univ. Michigan, Howard Hughes medical inst., dep. medicine, Ann Arbor MI 48109, United StatesDavid Ginsburg - Univ. Michigan, Howard Hughes medical inst., dep. medicine, Ann Arbor MI 48109, United States
- Resource Type
- Journal article
- Publication Details
- The Journal of immunology (1950), Vol.145(2), pp.768-777
- DOI
- 10.4049/jimmunol.145.2.768
- PMID
- 2114449
- NLM abbreviation
- J Immunol
- ISSN
- 0022-1767
- eISSN
- 1550-6606
- Publisher
- American Association of Immunologists
- Language
- English
- Date published
- 1990
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Pharmaceutical Sciences and Experimental Therapeutics; Internal Medicine
- Record Identifier
- 9984094579102771
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