The MHC Class I Associated Beta2-microglobulin (beta2m) Light Chain is Expressed in a Molar Excess Over HLA-ABC and CD1 on the Membrane of Leukaemic B Cells but not Leukaemic T Cells: Evidence for Further beta2m-Associated Molecules

Abstract

Beta 2-microglobulin (beta 2m) constitutes the common light chain of both the MHC-encoded HLA-ABC molecules and a group of structurally related glycoproteins recognized by antibodies of the first cluster of differentiation (CD1a, CD1b and CD1c). These CD1 antigens appear similar to murine T1 and Qa molecules in terms of structure and tissue distribution, although the question of inter-species homology is controversial. A further group of alloantigens expressed predominantly on T cells has been reported however, with immunogenetic characteristics more closely analogous to the murine T1/Qa system than the CD1 antigens, although their precise identity remains ill-defined. Having previously shown that malignant B cells may express membrane CD1c, we examined leukaemic B-cells corresponding to early lymphoblastic differentiation (null- and common acute lymphoblastic leukaemia) through to the terminal plasma cell stage for the expression of other non-HLA class I beta 2m-associated molecules. It was found that leukaemic B-cells at intermediate/late stages of differentiation, represented by non-Hodgkin's lymphoma (B-NHL) and 'hairy-cell' leukaemia (HCL), had significantly higher beta 2m:HLA-ABC ratios than did the cells from other types of B-cell malignancy. Although leukaemic B cells with a demonstrable non HLA-ABC-associated beta 2m component expressed detectable levels of CD1c, and insignificant levels of CD1a and CD1b, the antigen density was insufficient to account for the excess beta 2m. In vitro stimulation of leukaemic B cells by phorbol ester substantially increased the expression of HLA-ABC and CD1c, but also accentuated further the difference between the expression of these molecules and that of beta 2m. There was no detectable beta 2m other than that associated with HLA-ABC and CD1 on the surface of malignant T cells by contrast. Our findings strongly support the existence, at certain stages of leukaemic B-cell differentiation, of an additional beta 2m component(s) other than that associated with HLA-ABC and CD1.