Emergence of a B lymphocyte population with ADCC effector function in mammary tumor bearing mice

R. R. Padmanabhan, R. D. Paul, G. A. Watson, D. M. Lopez

Research output: Contribution to journalArticlepeer-review

3 Scopus citations

Abstract

Differential expression of antibody dependent cellular cytotoxicity (ADCC) effectors was studied in normal Balb/cCrgl mice and those bearing a chemically induced 7, 12 dimethylbenzanthracene mammary adenocarcinoma. Depletion of macrophages from normal mouse splenocytes by Sephadex G-10 columns resulted in elimination of ADCC. Further separation of the normal G-10 nonadherent splenocytes on nylon wool columns did not result in any population with significant cytotoxicity. However, Balb/c mice bearing mammary tumors showed enhanced levels of ADCC which were not eliminated by macrophage removal. Lymphocytes from tumor bearers further separated on nylon wool yielded nonadherent and adherent populations both capable of effecting significant ADCC. Treatment of the nylon nonadherent cells of both normal and tumor bearing mice with anti-asialo GM1 (AGM1) and complement decreased the ADCC responses. The same treatment only marginally affected cytotoxic levels of nylon adherent cells from tumor bearers, indicating that these effectors are primarily of non-NK lineage. In addition, G-10 nonadherent, nylon adherent cells from tumor bearers separated on a fluorescence activated cell sorter based on the presence of surface immunoglobulins (sIg) revealed that both the sIg- and sIg+ (98% pure) sorted cells were capable of functioning in ADCC. To determine whether in the tumor mice the 2% of sIg- cells present in the sIg+ sorted population were the ADCC effectors, mixing experiments were done in which up to 10% of sIg- cells from tumor bearers were added to nylon adherent cells from normal mice. No significant increases in ADCC levels were found over that of normal mice. These experiments indicate that the 2% sIg- cells were not the ADCC effectors nor were they inducing normal B cells to exert this type of cytotoxic reaction in vitro. To further substantiate the B cell lineage of the sIg+ ADCC effectors, surface immunoglobulins were removed with protease treatment. After a 36 hr incubation, 92% of the cells had regenerated their sIg. The results presented in this paper demonstrate that various splenic lymphoreticular populations from tumor bearers possess an enhanced cytolytic activity against antibody coated target cells. Among these is a unique nylon adherent sIg+ cell that is capable of functioning as an ADCC effector.

Original languageEnglish (US)
Pages (from-to)509-519
Number of pages11
JournalJournal of Leukocyte Biology
Volume43
Issue number6
DOIs
StatePublished - 1988

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Cell Biology

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