Sera from Multiparous Women Contain Antibodies Mediating Cytotoxicity against Breast Carcinoma Cells

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Abstract
Immunological mechanisms contributing to the epidemiologically established phenomenon of lower incidence of breast carcinoma among multiparous women and women with pregnancy at early age were searched for. Sera collected from 55 clinically healthy multiparous women were tested for the ability to mediate cytotoxicity in an antibody-dependent cell-mediated (ADCC) assay with normal blood leukocytes against 3 different [human] mammary carcinoma cell lines (MDA-MB 157, MDA-MB 231 and MDA-MB 436). Sera from 12 women (22%) mediated significant cytolysis against all 3 cell lines. Three additional sera were positive against MDA-MB 231 and 10 more against MDA-MB 436 (total 42%). Cross-adsorptions revealed that the ADCC-active sera contained antibodies that recognized the same antigen(s) on the different mammary carcinoma-derived cell lines. The sera from multiparous women contained no detectable ADCC-active antibodies against a [human] colon carcinoma cell line (SW 1116) or a [human] neuroblastoma cell line (SH-SY5Y). ADCC-active antibodies were found neither in sera from 35 nulliparous women nor in sera from 20 men. The ADCC-active antibodies against mammary carcinoma cells could not be removed by adsorption with lymphoblastoid cells established from the respective husbands of the multiparous women. This observation and the fact that the mammary carcinoma cell lines were established from different patients argue against an impact of HLA-related antigens. The ADCC-active antibodies might result from autoimmunization against some proliferation/differentiation antigen(s) of breast epithelium which is (are) expressed during pregnancy and lactation.