Defective expression of MHC class I antigens is frequent in B‐cell lymphomas of high‐grade malignancy

Abstract

An unselected series of 66 immunohistologically proven B-cell lymphomas was examined for the expression of MHC class I antigens with monoclonal antibodies directed against non-polymorphic determinants of HLA-A,B,C heavy chain and beta 2-microglobulin. The tumors were classified according to the Kiel classification. No significant differences were observed in the reaction for HLA-A,B,C and beta 2m which may be indicative of a coordinate expression in our lymphoma series. In 37 cases (56%), all tumor cells exhibited strong staining for class I antigens as observed in normal B cells. The remaining 29 cases (44%) showed abnormally low or undetectable class I expression in varying tumor cell subsets; 13 cases were completely devoid of HLA-A,B,C. Twenty-two out of 30 lymphomas of high-grade malignancy but only 7/36 lymphomas of low-grade malignancy presented defective class I expression. This difference in proportion is highly significant (p less than 0.00002). Eleven of the 13 class I-negative lymphomas belonged to the group of high-grade malignancy. Centrocytic lymphoma, which has the poorest prognosis among the B-cell lymphomas of low-grade malignancy, was defective in 40% of the cases examined. The lymphoblastic type represented an exception within the lymphomas of high-grade malignancy as no defective expression was observed. In addition to the correlation between the high-grade malignancy and defective class I expression, defects occurred more frequently in lymphomas with an extra-nodal primary manifestation (p less than 0.05). The grade of malignancy, however, was not correlated with the primary site of the lymphoma.

MedB-1, a human tumor cell line derived from a primary mediastinal large B-cell lymphoma

“…The HLA-D associated invariant chain, CD74, was cytoplasmically expressed in a subset of tumor cells in situ and in the cytoplasm of a major subset of MedB-1 cells but was not surface exposed. As is commonly found in primary mediastinal B-cell lymphomas, 21,22 the original tumor and the MedB-1 cell line completely lacked HLA-A,B,C products and ␤ 2 m which, in a B cell context, is highly abnormal. The immunophenotype of MedB-1 cells proved stable during the last nine years and, in essence, still corresponds to that of the parental lymphoma.…”

“…14 Med-B1 cells lack HLA-A,B,C ␣ heavy chains and ␤-2m, which is very often the case in mediastinal B-cell lymphoma. 1,21 This is also frequently encountered in mediastinal B-cell lymphoma. 1,22 Thus, the cell line features the very typical defect in major histocompatibility complex class I expression, the molecular mechanism of which remains elusive.…”

β-2 microglobulin: a prognostic factor in diffuse aggressive non-Hodgkin's lymphomas

“…Previous studies in non-Hodgkin's lymphoma have shown a correlation between stage of disease and P-2 microglobulin level (Spati et al, 1978;Child et al, 1980;Hagberg et al, 1983;Legros et al, 1987) (Moller et al, 1986), and that changes in HLA complex proteins which impair light and heavy chain association result in enhanced release of P-2 microglobulin (Ferrier et al, 1985;Rein et al, 1987).…”

Downregulation of major histocompatibility complex antigens in invading glioma cells: stealth invasion of the brain

“…[59][60][61][62][63] Tumor antigenspecific CD8 þ cytotoxic T cells recognize and destroy tumor cells carrying MHC class I antigens on their cell surface and are the main effectors against tumors in both human tumors and mouse models. 64 On the other hand, CD4 þ helper T cells recognize peptide antigens presented by MHC class II molecules.…”