Antibody-mediated proliferation of proximal tubule cells requires cross-linking of antigenic determinants.

In Heymann nephritis, the deposition in vivo of divalent anti-brush border antibodies on the luminal plasma membrane of proximal tubules leads to both epithelial cell proliferation and clumping and loss of microvilli. The passive transfer of divalent rat, sheep or rabbit anti-brush border antibodies to proteinuric recipients has a similar effect. To determine whether cross-linking of antigenic determinants in the plasma membrane was required to produce pathology, monovalent and divalent antibodies were compared for their ability to stimulate the incorporation of 3H-thymidine into kidney cells and to damage the brush border. Proximal tubule immunopathology was also evaluated in recipients treated with chlorpromazine, a drug which blocks the redistribution of plasma membrane molecules that may follow antibody-mediated cross-linking. Monovalent Fab fragments of anti-brush border antibodies failed to stimulate proximal tubule cell proliferation, and they appeared to block the proliferation induced by divalent antibodies. Destruction of microvilli also required the deposition of divalent antibodies. Chlorpromazine treatment prevented both the cell proliferation and the brush border loss produced by divalent antibodies, although clumping of microvilli was not prevented. Antibody-mediated cell proliferation and membrane shedding, resembling aspects of the normal B-cell response to ligands of the antigen receptor, might also account for tissue damage in autoimmune diseases affecting other epithelia.