B-CELL HOMOTYPIC ADHESION THROUGH EXON-A RESTRICTED EPITOPES OF CD45 INVOLVES LPA-1 ICAM-1, ICAM-3 INTERACTIONS, AND INDUCES COCLUSTERING OF CD45 AND LFA-1/

Lymphocyte interactions with other leukocytes and other cell types, as well as with components of the extracellular matrix, are one of the k ey steps in the immune response. Three novel monoclonal antibodies (Mo Abs) have been produced and selected for their ability to induce inter cellular adhesion in B cells. These three MoAbs immunoprecipitated a p olypeptide of 220 kD, displaying specific phosphotyrosine phosphatase activity th at has been identified as CD45. These MoAbs recognize epit opes located on the alternative spliced exon-A-encoded region of CD45. These epitopes are of polypeptidic nature, but they can be masked by addition of carbohydrate during CD45 biosynthesis. Interestingly enoug h, CD45 epitopes recognized by these MoAbs appeared to be selectively expressed on both peripheral blood and tonsillar B lymphocytes as well as on peripheral blood natural killer (NK) cells, CD45-mediated inter cellular adhesion was abrogated upon incubation with anti-leukocyte fu nction-associated antigen 1 (anti-LFA-1), intercellular cell adhesion molecule 1 (ICAM-1), and ICAM-3 MoAbs, thus indicating that this pheno menon involved both LFA-1/ICAM-1 and LFA-1/ICAM-3 cell adhesion pathwa ys. Moreover, CD45-mediated cell aggregation was also inhibited by pre incubation with some conventional anti-CD45 MoAbs. interestingly, the triggering of cell aggregation through CD45 induced membrane surface r elocation of CD45 and LFA-1 molecules, with both of them colocalizing at cell-cell contact areas of B-cell aggregates. Studies with inhibito rs of both phosphotyrosine phosphatase and tyrosine kinase activities suggest that CD45 phosphotyrosine phosphatase activity could be involv ed in CD45-mediated cell aggregation. Taken together, these results su pport the notion that CD45 is a key molecule in the regulation of LFA- 1-mediated cell-cell interactions. (C) 1995 by The American Society of Hematology.