DIFFERENTIAL CD45 ISOFORM EXPRESSION ACCOMPANIES REDUCED NATURAL ANTIBODY-BINDING IN L5178Y-F9 TUMOR PROGRESSION

Considerable evidence supports a role for polyclonal serum natural Ab (NAb) as a mediator of natural resistance against tumors, However, the molecular mechanisms of this NAb activity are not known. Flow cytomet ry selection of L5178Y-F9 murine T lymphoma cells for high NAb binding provided the variant LYNAb(+), which exhibited an inversely correspon ding reduction in tumorigenicity, Accompanying the increased NAb bindi ng, LYNAb(+) bound more monoclonal 14.8 anti-CD45RA and DNL-1.9 anti-C D45RC and less 13/2 anti-pan CD45, and the binding of MB23G2 anti-CD45 RB was eliminated, However, neuraminidase treatment increased NAb bind ing and detection of pan CD45, CD45RA, and CD45RC but reduced CD45RB e xpression, suggesting that the epitopes recognized by the former Abs a re masked by sialic acid, while the latter includes sialic acid, Growt h of the LYNAb(+) from a threshold s.c. inoculum in syngeneic DBA/2 mi ce yielded more tumorigenic cells which bound less NAb, anti-CD45RA, a nd anti-CD45RC; the same very low anti-CD45RB; and more anti-pan CD45. In accord with the mAb binding, the L5178Y-F9 and an in vivo passaged LYNAb(+) variant expressed predominantly lower m.w. CD45 isoforms whi le the LYNAb(+) expressed predominantly higher 200-kDa isoforms, The c onsistent correspondence between CD45RA and CD45 RC determinant expres sion, CD45 isoform expression, tumorigenicity, and NAb binding exhibit ed by T lymphoma cells selected for high NAb binding in vitro or throu gh tumor progression in vivo suggests that asialo high m.w. isoforms o f the cell surface-signaling molecule CD45 are differentially expresse d during tumor development and furthermore that they participate in NA b-mediated antitumor mechanisms.